發炎已經被證實會增加得癌症的風險，腫瘤微環境中所提供的細胞激素、生長因子或是趨化因子可以幫助癌細胞生長、促進皮細胞向間充質細胞轉化以及血管新生。然而，關於在癌症復發上癌細胞與腫瘤微環境之間的溝通，尤其是在抗癌藥物的反應下，仍然是不清楚的。首先，我們發現在腫瘤相關纖維母細胞中的CEBPD會受到發炎因子(前列腺素、腫瘤壞死因子-α和白细胞介素-1B)以及抗癌藥物(順鉑和5-氟尿嘧啶)活化，進而導致腫瘤侵襲、轉移、抗藥性與增加癌幹原性。特別的是我們之前研究顯示CEBPD所誘導產生的PTX3有參與在巨噬細胞促進癌症的進程上，其中機制是透過預防巨噬細胞吞噬癌細胞的方式來達到促進癌症的效果。再加上PTX3在許多癌症上被認為是癌症生物標記，但是關於PTX3調控癌症進展的機制仍是不清楚的。因此我們深入探討是否PTX3在腫瘤相關纖維母細胞中是一種CEBPD的反應基因並且有促腫瘤的作用。結果顯示CEBPD 可直接透過啟動子調節PTX3轉錄的表達，並且我們也透過DNA結合測定法發現抗癌藥物也可以增加CEBPD結合於PTX3啟動子上。有趣的是我們發現原核重組PTX3蛋白的C端與哺乳動物重組PTX3蛋白的C端有著完全相反的致癌反應。根據原核重組PTX3蛋白的C端，我們縮短以及設計小分子胜肽用以阻斷哺乳動物PTX3所產生的腫瘤侵襲、轉移、抗藥性與癌幹原性，並且也在動物實驗上得到抗癌症的效果。我們發現 RI37胜肽抑制劑可以用於抑制癌症生長和控制侵襲、轉移和抗藥性癌進展的藥物。我們研究中除了提供PTX3在癌細胞和癌周邊組織之間的相互作用，也利用此論點開發出RI37胜肽抑制劑，其效果能有效降低癌細胞的侵襲、轉移和抗藥性的風險。

Inflammation has been demonstrated to increase the risk of cancer by providing various cytokines, growth factors or chemokines from the tumor microenvironment that maintain a sustained proliferative rate, promote epithelial-mesenchymal transition (EMT) and facilitate angiogenesis. However, the communication between cancer cells and the microenvironmentin on cancer recurrence, especially in response to anticancer drugs, remains obscure. To begin with, we found that increased abundance of CCAAT/enhancer binding protein delta (CEBPD) in myofibroblasts/cancer-associated fibroblasts (CAFs) in response to inflammatory cytokines (prostaglandin E2, TNFα and IL-1β) and anticancer drugs (cisplatin and 5-fluorouracil), and further contributed to metastasis, invasion, chemoresistance and stemness of breast cancer cells. Particularly, we previously demonstrated that CEBPD-induced PTX3 in macrophages promotes cancer progression by preventing the macrophage-mediated phagocytosis of tumor cells. Then, PTX3 has been considered to play a novel biomarker in various cancers, but the cancer-related mechanism is still unknown. To address whether PTX3 is a CEBPD responsive gene and serves as a protumor role in CAFs upon anticancer drug treatment. We found CEBPD can directly regulate PTX3 transcription through promoter regulation. Additional, an in vivo DNA binding assay further showed that the binding of CEBPD to the PTX3 promoter was induced upon anticancer drugs treatment. Interestingly, we identified that the C-terminus of prokaryotic recombinant PTX3 protein showed an opposite tumorigenic effect to the mammalian PTX3. According to the sequence of C-terminus of prokaryotic recombinant PTX3, we narrowed down and designed peptides for blocking mammalian PTX3-induced metastasis, invasion, chemoresistance and stemness of breast cancer cells. RI37 peptide was assessed the antitumor effects by in vivo assays. RI37 could function as a promising inhibitor for preventing cancer progression and metastasis, invasion and progression of drug-resistant cancers. The identification of PTX3 provided a new insight in the interaction between tumor and its host. The RI37 peptide showed a great opportunity to largely reduce the risk of invasion and metastasis of cancer and drug-resistant cancers.

1. Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98-101.
2. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature reviews Cancer. 2003;3(6):453-8.
3. Gao D, Vahdat LT, Wong S, Chang JC, and Mittal V. Microenvironmental regulation of epithelial-mesenchymal transitions in cancer. Cancer research. 2012;72(19):4883-9.
4. Kalluri R, and Zeisberg M. Fibroblasts in cancer. Nature reviews Cancer. 2006;6(5):392-401.
5. Chang HY, Chi JT, Dudoit S, Bondre C, van de Rijn M, Botstein D, and Brown PO. Diversity, topographic differentiation, and positional memory in human fibroblasts. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(20):12877-82.
6. Desmouliere A, Geinoz A, Gabbiani F, and Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. The Journal of cell biology. 1993;122(1):103-11.
7. Grinnell F. Fibroblasts, myofibroblasts, and wound contraction. The Journal of cell biology. 1994;124(4):401-4.
8. Ronnov-Jessen L, Petersen OW, Koteliansky VE, and Bissell MJ. The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. The Journal of clinical investigation. 1995;95(2):859-73.
9. Karvonen HM, Lehtonen ST, Sormunen RT, Lappi-Blanco E, Skold CM, and Kaarteenaho RL. Lung cancer-associated myofibroblasts reveal distinctive ultrastructure and function. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9(5):664-74.
10. Orimo A, Tomioka Y, Shimizu Y, Sato M, Oigawa S, Kamata K, Nogi Y, Inoue S, Takahashi M, Hata T, et al. Cancer-associated myofibroblasts possess various factors to promote endometrial tumor progression. Clinical cancer research : an official journal of the American Association for Cancer Research. 2001;7(10):3097-105.
11. Shain KH, and Dalton WS. Environmental-mediated drug resistance: a target for multiple myeloma therapy. Expert review of hematology. 2009;2(6):649-62.
12. Sounni NE, and Noel A. Targeting the tumor microenvironment for cancer therapy. Clinical chemistry. 2013;59(1):85-93.
13. Rodemann HP, and Muller GA. Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. American journal of kidney diseases : the official journal of the National Kidney Foundation. 1991;17(6):684-6.
14. Nakamura T, Matsumoto K, Kiritoshi A, Tano Y, and Nakamura T. Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions. Cancer research. 1997;57(15):3305-13.
15. Parsonage G, Filer AD, Haworth O, Nash GB, Rainger GE, Salmon M, and Buckley CD. A stromal address code defined by fibroblasts. Trends in immunology. 2005;26(3):150-6.
16. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, and Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nature reviews Molecular cell biology. 2002;3(5):349-63.
17. Simian M, Hirai Y, Navre M, Werb Z, Lochter A, and Bissell MJ. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development (Cambridge, England). 2001;128(16):3117-31.
18. Wiseman BS, and Werb Z. Stromal effects on mammary gland development and breast cancer. Science (New York, NY). 2002;296(5570):1046-9.
19. Bissell MJ, and Radisky D. Putting tumours in context. Nature reviews Cancer. 2001;1(1):46-54.
20. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, and Cunha GR. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer research. 1999;59(19):5002-11.
21. Dumont N, Liu B, Defilippis RA, Chang H, Rabban JT, Karnezis AN, Tjoe JA, Marx J, Parvin B, and Tlsty TD. Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics. Neoplasia (New York, NY). 2013;15(3):249-62.
22. Marsh T, Pietras K, and McAllister SS. Fibroblasts as architects of cancer pathogenesis. Biochimica et biophysica acta. 2013;1832(7):1070-8.
23. Erez N, Truitt M, Olson P, Arron ST, and Hanahan D. Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer cell. 2010;17(2):135-47.
24. Franco OE, Shaw AK, Strand DW, and Hayward SW. Cancer associated fibroblasts in cancer pathogenesis. Seminars in cell & developmental biology. 2010;21(1):33-9.
25. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL, and Weinberg RA. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 2005;121(3):335-48.
26. Rasanen K, and Vaheri A. Activation of fibroblasts in cancer stroma. Experimental cell research. 2010;316(17):2713-22.
27. Chaffer CL, and Weinberg RA. A perspective on cancer cell metastasis. Science (New York, NY). 2011;331(6024):1559-64.
28. Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, Harrington K, Williamson P, Moeendarbary E, Charras G, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nature cell biology. 2013;15(6):637-46.
29. Fukumura D, Xavier R, Sugiura T, Chen Y, Park EC, Lu N, Selig M, Nielsen G, Taksir T, Jain RK, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell. 1998;94(6):715-25.
30. Zhang XH, Jin X, Malladi S, Zou Y, Wen YH, Brogi E, Smid M, Foekens JA, and Massague J. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell. 2013;154(5):1060-73.
31. Sotgia F, Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, and Lisanti MP. Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment. Breast cancer research : BCR. 2011;13(4):213.
32. Siegel R, Naishadham D, and Jemal A. Cancer statistics, 2012. CA: a cancer journal for clinicians. 2012;62(1):10-29.
33. Place AE, Jin Huh S, and Polyak K. The microenvironment in breast cancer progression: biology and implications for treatment. Breast cancer research : BCR. 2011;13(6):227.
34. Siveen KS, and Kuttan G. Role of macrophages in tumour progression. Immunology letters. 2009;123(2):97-102.
35. Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, van't Veer LJ, and Perou CM. Concordance among gene-expression-based predictors for breast cancer. The New England journal of medicine. 2006;355(6):560-9.
36. Kalluri R, and Weinberg RA. The basics of epithelial-mesenchymal transition. The Journal of clinical investigation. 2009;119(6):1420-8.
37. Schedin P, and Borges V. Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women's breast cancer. Breast cancer research : BCR. 2009;11(2):102.
38. Loeffler M, Kruger JA, Niethammer AG, and Reisfeld RA. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. The Journal of clinical investigation. 2006;116(7):1955-62.
39. Martinez-Outschoorn UE, Goldberg A, Lin Z, Ko YH, Flomenberg N, Wang C, Pavlides S, Pestell RG, Howell A, Sotgia F, et al. Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. Cancer biology & therapy. 2011;12(10):924-38.
40. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, and Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(7):3983-8.
41. Medema JP, and Vermeulen L. Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature. 2011;474(7351):318-26.
42. Shestopalov IA, and Zon LI. Stem cells: The right neighbour. Nature. 2012;481(7382):453-5.
43. Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F, Korkaya H, Heath A, Dutcher J, Kleer CG, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer research. 2011;71(2):614-24.
44. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nature cell biology. 2010;12(5):468-76.
45. Boelens MC, Wu TJ, Nabet BY, Xu B, Qiu Y, Yoon T, Azzam DJ, Twyman-Saint Victor C, Wiemann BZ, Ishwaran H, et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 2014;159(3):499-513.
46. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131(6):1109-23.
47. Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. Journal of the National Cancer Institute. 2008;100(9):672-9.
48. Thiery JP, and Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nature reviews Molecular cell biology. 2006;7(2):131-42.
49. Haraguchi M, Okubo T, Miyashita Y, Miyamoto Y, Hayashi M, Crotti TN, McHugh KP, and Ozawa M. Snail regulates cell-matrix adhesion by regulation of the expression of integrins and basement membrane proteins. The Journal of biological chemistry. 2008;283(35):23514-23.
50. Huber MA, Kraut N, and Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Current opinion in cell biology. 2005;17(5):548-58.
51. Thiery JP, Acloque H, Huang RY, and Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871-90.
52. Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zurrer-Hardi U, Bell G, et al. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 2012;148(5):1015-28.
53. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704-15.
54. Sun Y, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, and Nelson PS. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nature medicine. 2012;18(9):1359-68.
55. Presta M, Camozzi M, Salvatori G, and Rusnati M. Role of the soluble pattern recognition receptor PTX3 in vascular biology. Journal of cellular and molecular medicine. 2007;11(4):723-38.
56. Garlanda C, Bottazzi B, Bastone A, and Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annual review of immunology. 2005;23(337-66.
57. Jaillon S, Peri G, Delneste Y, Fremaux I, Doni A, Moalli F, Garlanda C, Romani L, Gascan H, Bellocchio S, et al. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. The Journal of experimental medicine. 2007;204(4):793-804.
58. Cotena A, Maina V, Sironi M, Bottazzi B, Jeannin P, Vecchi A, Corvaia N, Daha MR, Mantovani A, and Garlanda C. Complement dependent amplification of the innate response to a cognate microbial ligand by the long pentraxin PTX3. Journal of immunology (Baltimore, Md : 1950). 2007;179(9):6311-7.
59. Bottazzi B, Garlanda C, Cotena A, Moalli F, Jaillon S, Deban L, and Mantovani A. The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunological reviews. 2009;227(1):9-18.
60. Kunes P, Lonsky V, Mand'ak J, Brtko M, Kolackova M, Andrys C, Kudlova M, and Krejsek J. Essential PTX3 biology (not only) for cardiologists and cardiac surgeons. Acta medica (Hradec Kralove) / Universitas Carolina, Facultas Medica Hradec Kralove. 2007;50(1):29-33.
61. Rusnati M, Camozzi M, Moroni E, Bottazzi B, Peri G, Indraccolo S, Amadori A, Mantovani A, and Presta M. Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis. Blood. 2004;104(1):92-9.
62. Deban L, Russo RC, Sironi M, Moalli F, Scanziani M, Zambelli V, Cuccovillo I, Bastone A, Gobbi M, Valentino S, et al. Regulation of leukocyte recruitment by the long pentraxin PTX3. Nature immunology. 2010;11(4):328-34.
63. Nebuloni M, Pasqualini F, Zerbi P, Lauri E, Mantovani A, Vago L, and Garlanda C. PTX3 expression in the heart tissues of patients with myocardial infarction and infectious myocarditis. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 2011;20(1):e27-35.
64. Breviario F, d'Aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M, et al. Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. The Journal of biological chemistry. 1992;267(31):22190-7.
65. Chang LH, Huang HS, Wu PT, Jou IM, Pan MH, Chang WC, Wang DD, and Wang JM. Role of macrophage CCAAT/enhancer binding protein delta in the pathogenesis of rheumatoid arthritis in collagen-induced arthritic mice. PloS one. 2012;7(9):e45378.
66. Luchetti MM, Piccinini G, Mantovani A, Peri G, Matteucci C, Pomponio G, Fratini M, Fraticelli P, Sambo P, Di Loreto C, et al. Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clinical and experimental immunology. 2000;119(1):196-202.
67. Iwata Y, Yoshizaki A, Ogawa F, Komura K, Hara T, Muroi E, Takenaka M, Shimizu K, Hasegawa M, Fujimoto M, et al. Increased serum pentraxin 3 in patients with systemic sclerosis. The Journal of rheumatology. 2009;36(5):976-83.
68. Fazzini F, Peri G, Doni A, Dell'Antonio G, Dal Cin E, Bozzolo E, D'Auria F, Praderio L, Ciboddo G, Sabbadini MG, et al. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis and rheumatism. 2001;44(12):2841-50.
69. Mauri T, Bellani G, Patroniti N, Coppadoro A, Peri G, Cuccovillo I, Cugno M, Iapichino G, Gattinoni L, Pesenti A, et al. Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive care medicine. 2010;36(4):621-9.
70. Yilmaz MI, Sonmez A, Ortiz A, Saglam M, Kilic S, Eyileten T, Caglar K, Oguz Y, Vural A, Cakar M, et al. Soluble TWEAK and PTX3 in nondialysis CKD patients: impact on endothelial dysfunction and cardiovascular outcomes. Clinical journal of the American Society of Nephrology : CJASN. 2011;6(4):785-92.
71. Pepys MB, and Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Advances in immunology. 1983;34(141-212.
72. Goodman AR, Cardozo T, Abagyan R, Altmeyer A, Wisniewski HG, and Vilcek J. Long pentraxins: an emerging group of proteins with diverse functions. Cytokine & growth factor reviews. 1996;7(2):191-202.
73. Inforzato A, Peri G, Doni A, Garlanda C, Mantovani A, Bastone A, Carpentieri A, Amoresano A, Pucci P, Roos A, et al. Structure and function of the long pentraxin PTX3 glycosidic moiety: fine-tuning of the interaction with C1q and complement activation. Biochemistry. 2006;45(38):11540-51.
74. Introna M, Alles VV, Castellano M, Picardi G, De Gioia L, Bottazzai B, Peri G, Breviario F, Salmona M, De Gregorio L, et al. Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites. Blood. 1996;87(5):1862-72.
75. Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, Spreafico F, Pausa M, D'Ettorre C, Gianazza E, et al. Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component. The Journal of biological chemistry. 1997;272(52):32817-23.
76. Inforzato A, Reading PC, Barbati E, Bottazzi B, Garlanda C, and Mantovani A. The "sweet" side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation. Frontiers in immunology. 2012;3(407.
77. Roumenina LT, Ruseva MM, Zlatarova A, Ghai R, Kolev M, Olova N, Gadjeva M, Agrawal A, Bottazzi B, Mantovani A, et al. Interaction of C1q with IgG1, C-reactive protein and pentraxin 3: mutational studies using recombinant globular head modules of human C1q A, B, and C chains. Biochemistry. 2006;45(13):4093-104.
78. Nauta AJ, Daha MR, van Kooten C, and Roos A. Recognition and clearance of apoptotic cells: a role for complement and pentraxins. Trends in immunology. 2003;24(3):148-54.
79. Gout E, Moriscot C, Doni A, Dumestre-Perard C, Lacroix M, Perard J, Schoehn G, Mantovani A, Arlaud GJ, and Thielens NM. M-ficolin interacts with the long pentraxin PTX3: a novel case of cross-talk between soluble pattern-recognition molecules. Journal of immunology (Baltimore, Md : 1950). 2011;186(10):5815-22.
80. Ma YJ, Doni A, Hummelshoj T, Honore C, Bastone A, Mantovani A, Thielens NM, and Garred P. Synergy between ficolin-2 and pentraxin 3 boosts innate immune recognition and complement deposition. The Journal of biological chemistry. 2009;284(41):28263-75.
81. Ma YJ, Doni A, Skjoedt MO, Honore C, Arendrup M, Mantovani A, and Garred P. Heterocomplexes of mannose-binding lectin and the pentraxins PTX3 or serum amyloid P component trigger cross-activation of the complement system. The Journal of biological chemistry. 2011;286(5):3405-17.
82. Bottazzi B, Doni A, Garlanda C, and Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annual review of immunology. 2010;28(157-83.
83. Braunschweig A, and Jozsi M. Human pentraxin 3 binds to the complement regulator c4b-binding protein. PloS one. 2011;6(8):e23991.
84. Deban L, Jarva H, Lehtinen MJ, Bottazzi B, Bastone A, Doni A, Jokiranta TS, Mantovani A, and Meri S. Binding of the long pentraxin PTX3 to factor H: interacting domains and function in the regulation of complement activation. Journal of immunology (Baltimore, Md : 1950). 2008;181(12):8433-40.
85. Dias AA, Goodman AR, Dos Santos JL, Gomes RN, Altmeyer A, Bozza PT, Horta MF, Vilcek J, and Reis LF. TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis. Journal of leukocyte biology. 2001;69(6):928-36.
86. Ravizza T, Moneta D, Bottazzi B, Peri G, Garlanda C, Hirsch E, Richards GJ, Mantovani A, and Vezzani A. Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: evidence for a protective role in seizure-induced neurodegeneration. Neuroscience. 2001;105(1):43-53.
87. Camozzi M, Zacchigna S, Rusnati M, Coltrini D, Ramirez-Correa G, Bottazzi B, Mantovani A, Giacca M, and Presta M. Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. Arteriosclerosis, thrombosis, and vascular biology. 2005;25(9):1837-42.
88. Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, Doni A, Bastone A, Mantovani G, Beck Peccoz P, et al. PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development (Cambridge, England). 2004;131(7):1577-86.
89. Scarchilli L, Camaioni A, Bottazzi B, Negri V, Doni A, Deban L, Bastone A, Salvatori G, Mantovani A, Siracusa G, et al. PTX3 interacts with inter-alpha-trypsin inhibitor: implications for hyaluronan organization and cumulus oophorus expansion. The Journal of biological chemistry. 2007;282(41):30161-70.
90. Camozzi M, Rusnati M, Bugatti A, Bottazzi B, Mantovani A, Bastone A, Inforzato A, Vincenti S, Bracci L, Mastroianni D, et al. Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3. The Journal of biological chemistry. 2006;281(32):22605-13.
91. Sardana G, Jung K, Stephan C, and Diamandis EP. Proteomic analysis of conditioned media from the PC3, LNCaP, and 22Rv1 prostate cancer cell lines: discovery and validation of candidate prostate cancer biomarkers. Journal of proteome research. 2008;7(8):3329-38.
92. Diamandis EP, Goodglick L, Planque C, and Thornquist MD. Pentraxin-3 is a novel biomarker of lung carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011;17(8):2395-9.
93. Willeke F, Assad A, Findeisen P, Schromm E, Grobholz R, von Gerstenbergk B, Mantovani A, Peri S, Friess HH, Post S, et al. Overexpression of a member of the pentraxin family (PTX3) in human soft tissue liposarcoma. European journal of cancer (Oxford, England : 1990). 2006;42(15):2639-46.
94. Kondo S, Ueno H, Hosoi H, Hashimoto J, Morizane C, Koizumi F, Tamura K, and Okusaka T. Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma. British journal of cancer. 2013;109(3):739-46.
95. Pavlou MP, Dimitromanolakis A, and Diamandis EP. Coupling proteomics and transcriptomics in the quest of subtype-specific proteins in breast cancer. Proteomics. 2013;13(7):1083-95.
96. Hsiao YW, Li CF, Chi JY, Tseng JT, Chang Y, Hsu LJ, Lee CH, Chang TH, Wang SM, Wang DD, et al. CCAAT/enhancer binding protein delta in macrophages contributes to immunosuppression and inhibits phagocytosis in nasopharyngeal carcinoma. Science signaling. 2013;6(284):ra59.
97. Locatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, Bello L, Valentino S, Barbati E, Nebuloni M, et al. The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas. Journal of neuroimmunology. 2013;260(1-2):99-106.
98. Wu Z, Bucher NL, and Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Molecular and cellular biology. 1996;16(8):4128-36.
99. Scott LM, Civin CI, Rorth P, and Friedman AD. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood. 1992;80(7):1725-35.
100. Cardinaux JR, and Magistretti PJ. Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP-regulated glycogen metabolism. The Journal of neuroscience : the official journal of the Society for Neuroscience. 1996;16(3):919-29.
101. Zannetti C, Bonnay F, Takeshita F, Parroche P, Menetrier-Caux C, Tommasino M, and Hasan UA. C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. The Journal of biological chemistry. 2010;285(45):34773-80.
102. Ramji DP, and Foka P. CCAAT/enhancer-binding proteins: structure, function and regulation. The Biochemical journal. 2002;365(Pt 3):561-75.
103. Ko CY, Chang WC, and Wang JM. Biological roles of CCAAT/Enhancer-binding protein delta during inflammation. Journal of biomedical science. 2015;22(6.
104. Lekstrom-Himes J, and Xanthopoulos KG. Biological role of the CCAAT/enhancer-binding protein family of transcription factors. The Journal of biological chemistry. 1998;273(44):28545-8.
105. Luedde T, Duderstadt M, Streetz KL, Tacke F, Kubicka S, Manns MP, and Trautwein C. C/EBP beta isoforms LIP and LAP modulate progression of the cell cycle in the regenerating mouse liver. Hepatology (Baltimore, Md). 2004;40(2):356-65.
106. Balamurugan K, and Sterneck E. The many faces of C/EBPdelta and their relevance for inflammation and cancer. International journal of biological sciences. 2013;9(9):917-33.
107. Sato Y, Nishio Y, Sekine O, Kodama K, Nagai Y, Nakamura T, Maegawa H, and Kashiwagi A. Increased expression of CCAAT/enhancer binding protein-beta and -delta and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats. Diabetologia. 2007;50(2):481-9.
108. O'Rourke J, Yuan R, and DeWille J. CCAAT/enhancer-binding protein-delta (C/EBP-delta) is induced in growth-arrested mouse mammary epithelial cells. The Journal of biological chemistry. 1997;272(10):6291-6.
109. Gery S, Tanosaki S, Hofmann WK, Koppel A, and Koeffler HP. C/EBPdelta expression in a BCR-ABL-positive cell line induces growth arrest and myeloid differentiation. Oncogene. 2005;24(9):1589-97.
110. Ikezoe T, Gery S, Yin D, O'Kelly J, Binderup L, Lemp N, Taguchi H, and Koeffler HP. CCAAT/enhancer-binding protein delta: a molecular target of 1,25-dihydroxyvitamin D3 in androgen-responsive prostate cancer LNCaP cells. Cancer research. 2005;65(11):4762-8.
111. Thangaraju M, Rudelius M, Bierie B, Raffeld M, Sharan S, Hennighausen L, Huang AM, and Sterneck E. C/EBPdelta is a crucial regulator of pro-apoptotic gene expression during mammary gland involution. Development (Cambridge, England). 2005;132(21):4675-85.
112. Kitami Y, Fukuoka T, Hiwada K, and Inagami T. A high level of CCAAT-enhancer binding protein-delta expression is a major determinant for markedly elevated differential gene expression of the platelet-derived growth factor-alpha receptor in vascular smooth muscle cells of genetically hypertensive rats. Circulation research. 1999;84(1):64-73.
113. Yang ZH, Kitami Y, Takata Y, Okura T, and Hiwada K. Targeted overexpression of CCAAT/enhancer-binding protein-delta evokes enhanced gene transcription of platelet-derived growth factor alpha-receptor in vascular smooth muscle cells. Circulation research. 2001;89(6):503-8.
114. Tang D, Sivko GS, and DeWille JW. Promoter methylation reduces C/EBPdelta (CEBPD) gene expression in the SUM-52PE human breast cancer cell line and in primary breast tumors. Breast cancer research and treatment. 2006;95(2):161-70.
115. Agrawal S, Hofmann WK, Tidow N, Ehrich M, van den Boom D, Koschmieder S, Berdel WE, Serve H, and Muller-Tidow C. The C/EBPdelta tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood. 2007;109(9):3895-905.
116. Ko CY, Hsu HC, Shen MR, Chang WC, and Wang JM. Epigenetic silencing of CCAAT/enhancer-binding protein delta activity by YY1/polycomb group/DNA methyltransferase complex. The Journal of biological chemistry. 2008;283(45):30919-32.
117. Porter DA, Krop IE, Nasser S, Sgroi D, Kaelin CM, Marks JR, Riggins G, and Polyak K. A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer research. 2001;61(15):5697-702.
118. Balamurugan K, Wang JM, Tsai HH, Sharan S, Anver M, Leighty R, and Sterneck E. The tumour suppressor C/EBPdelta inhibits FBXW7 expression and promotes mammary tumour metastasis. The EMBO journal. 2010;29(24):4106-17.
119. Wu SR, Li CF, Hung LY, Huang AM, Tseng JT, Tsou JH, and Wang JM. CCAAT/enhancer-binding protein delta mediates tumor necrosis factor alpha-induced Aurora kinase C transcription and promotes genomic instability. The Journal of biological chemistry. 2011;286(33):28662-70.
120. Min Y, Ghose S, Boelte K, Li J, Yang L, and Lin PC. C/EBP-delta regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1alpha. Oncogene. 2011;30(49):4901-9.
121. Cooper LA, Gutman DA, Chisolm C, Appin C, Kong J, Rong Y, Kurc T, Van Meir EG, Saltz JH, Moreno CS, et al. The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma. The American journal of pathology. 2012;180(5):2108-19.
122. Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, Sulman EP, Anne SL, Doetsch F, Colman H, et al. The transcriptional network for mesenchymal transformation of brain tumours. Nature. 2010;463(7279):318-25.
123. Hour TC, Lai YL, Kuan CI, Chou CK, Wang JM, Tu HY, Hu HT, Lin CS, Wu WJ, Pu YS, et al. Transcriptional up-regulation of SOD1 by CEBPD: a potential target for cisplatin resistant human urothelial carcinoma cells. Biochemical pharmacology. 2010;80(3):325-34.
124. Wang YH, Wu WJ, Wang WJ, Huang HY, Li WM, Yeh BW, Wu TF, Shiue YL, Sheu JJ, Wang JM, et al. CEBPD amplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis. Oncotarget. 2015;6(31):31069-84.
125. Wang WJ, Li CF, Chu YY, Wang YH, Hour TC, Yen CJ, Chang WC, and Wang JM. Inhibition of EGFR/STAT3/CEBPD axis reverses cisplatin cross-resistance with paclitaxel in urothelial carcinoma of urinary bladder. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016.
126. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, and Langer R. Nanocarriers as an emerging platform for cancer therapy. Nature nanotechnology. 2007;2(12):751-60.
127. Dong J, Zeng BH, Xu LH, Wang JY, Li MZ, Zeng MS, and Liu WL. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma. Journal of translational medicine. 2010;8(81.
128. Kang TH, Mao CP, He L, Tsai YC, Liu K, La V, Wu TC, and Hung CF. Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects. PloS one. 2012;7(4):e35141.
129. Enback J, and Laakkonen P. Tumour-homing peptides: tools for targeting, imaging and destruction. Biochemical Society transactions. 2007;35(Pt 4):780-3.
130. Dorsam RT, and Gutkind JS. G-protein-coupled receptors and cancer. Nature reviews Cancer. 2007;7(2):79-94.
131. Aina OH, Sroka TC, Chen ML, and Lam KS. Therapeutic cancer targeting peptides. Biopolymers. 2002;66(3):184-99.
132. Shadidi M, and Sioud M. Selective targeting of cancer cells using synthetic peptides. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2003;6(6):363-71.
133. Van Meter ME, and Kim ES. Bevacizumab: current updates in treatment. Current opinion in oncology. 2010;22(6):586-91.
134. Boross P, Lohse S, Nederend M, Jansen JH, van Tetering G, Dechant M, Peipp M, Royle L, Liew LP, Boon L, et al. IgA EGFR antibodies mediate tumour killing in vivo. EMBO molecular medicine. 2013;5(8):1213-26.
135. Modjtahedi H, Ali S, and Essapen S. Therapeutic application of monoclonal antibodies in cancer: advances and challenges. British medical bulletin. 2012;104(41-59.
136. Gottesman MM. Mechanisms of cancer drug resistance. Annual review of medicine. 2002;53(615-27.
137. Lee S, Xie J, and Chen X. Peptides and peptide hormones for molecular imaging and disease diagnosis. Chemical reviews. 2010;110(5):3087-111.
138. Chen K, Sun X, Niu G, Ma Y, Yap LP, Hui X, Wu K, Fan D, Conti PS, and Chen X. Evaluation of 64Cu labeled GX1: a phage display peptide probe for PET imaging of tumor vasculature. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 2012;14(1):96-105.
139. Chen K, and Conti PS. Target-specific delivery of peptide-based probes for PET imaging. Advanced drug delivery reviews. 2010;62(11):1005-22.
140. Lin ZY, Chuang YH, and Chuang WL. Cancer-associated fibroblasts up-regulate CCL2, CCL26, IL6 and LOXL2 genes related to promotion of cancer progression in hepatocellular carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2012;66(7):525-9.
141. Tessarollo L. Manipulating mouse embryonic stem cells. Methods in molecular biology (Clifton, NJ). 2001;158(47-63.
142. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, Wadhwani N, Keil SD, Junaid SA, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer discovery. 2011;1(1):54-67.
143. Wang JM, Ko CY, Chen LC, Wang WL, and Chang WC. Functional role of NF-IL6beta and its sumoylation and acetylation modifications in promoter activation of cyclooxygenase 2 gene. Nucleic acids research. 2006;34(1):217-31.
144. Tai HC, Huang HY, Lee SW, Lin CY, Sheu MJ, Chang SL, Wu LC, Shiue YL, Wu WR, Lin CM, et al. Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma. Journal of clinical pathology. 2012;65(3):248-53.
145. Wu KJ, and Yang MH. Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection. Bioscience reports. 2011;31(6):449-55.
146. Pan YC, Li CF, Ko CY, Pan MH, Chen PJ, Tseng JT, Wu WC, Chang WC, Huang AM, Sterneck E, et al. CEBPD reverses RB/E2F1-mediated gene repression and participates in HMDB-induced apoptosis of cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010;16(23):5770-80.
147. Cantwell CA, Sterneck E, and Johnson PF. Interleukin-6-specific activation of the C/EBPdelta gene in hepatocytes is mediated by Stat3 and Sp1. Molecular and cellular biology. 1998;18(4):2108-17.
148. Sanford DC, and DeWille JW. C/EBPdelta is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cells. The Prostate. 2005;63(2):143-54.
149. Alam T, An MR, and Papaconstantinou J. Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response. The Journal of biological chemistry. 1992;267(8):5021-4.
150. Tengku-Muhammad TS, Hughes TR, Ranki H, Cryer A, and Ramji DP. Differential regulation of macrophage CCAAT-enhancer binding protein isoforms by lipopolysaccharide and cytokines. Cytokine. 2000;12(9):1430-6.
151. Yin M, Yang SQ, Lin HZ, Lane MD, Chatterjee S, and Diehl AM. Tumor necrosis factor alpha promotes nuclear localization of cytokine-inducible CCAAT/enhancer binding protein isoforms in hepatocytes. The Journal of biological chemistry. 1996;271(30):17974-8.
152. Ji C, Chang W, Centrella M, and McCarthy TL. Activation domains of CCAAT enhancer binding protein delta: regions required for native activity and prostaglandin E2-dependent transactivation of insulin-like growth factor I gene expression in rat osteoblasts. Molecular endocrinology (Baltimore, Md). 2003;17(9):1834-43.
153. Mueller MM, and Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nature reviews Cancer. 2004;4(11):839-49.
154. Cunha GR, Hayward SW, Wang YZ, and Ricke WA. Role of the stromal microenvironment in carcinogenesis of the prostate. International journal of cancer. 2003;107(1):1-10.
155. Ronca R, Giacomini A, Di Salle E, Coltrini D, Pagano K, Ragona L, Matarazzo S, Rezzola S, Maiolo D, Torrella R, et al. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. Cancer cell. 2015;28(2):225-39.
156. Iwasaki A, and Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science (New York, NY). 2010;327(5963):291-5.
157. da Silva Correia J, and Ulevitch RJ. MD-2 and TLR4 N-linked glycosylations are important for a functional lipopolysaccharide receptor. The Journal of biological chemistry. 2002;277(3):1845-54.
158. Weber AN, Morse MA, and Gay NJ. Four N-linked glycosylation sites in human toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion. The Journal of biological chemistry. 2004;279(33):34589-94.
159. Sun J, Duffy KE, Ranjith-Kumar CT, Xiong J, Lamb RJ, Santos J, Masarapu H, Cunningham M, Holzenburg A, Sarisky RT, et al. Structural and functional analyses of the human Toll-like receptor 3. Role of glycosylation. The Journal of biological chemistry. 2006;281(16):11144-51.
160. Jeannin P, Bottazzi B, Sironi M, Doni A, Rusnati M, Presta M, Maina V, Magistrelli G, Haeuw JF, Hoeffel G, et al. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity. 2005;22(5):551-60.
161. Lu J, Marnell LL, Marjon KD, Mold C, Du Clos TW, and Sun PD. Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature. 2008;456(7224):989-92.
162. Moalli F, Doni A, Deban L, Zelante T, Zagarella S, Bottazzi B, Romani L, Mantovani A, and Garlanda C. Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus. Blood. 2010;116(24):5170-80.
163. Chen WY, Wu F, You ZY, Zhang ZM, Guo YL, and Zhong LX. Analyzing the differentially expressed genes and pathway cross-talk in aggressive breast cancer. The journal of obstetrics and gynaecology research. 2015;41(1):132-40.
164. Menyhart O, Santarpia L, and Gyorffy B. A Comprehensive Outline of Trastuzumab Resistance Biomarkers in HER2 Overexpressing Breast Cancer. Current cancer drug targets. 2015;15(8):665-83.
165. Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A, and Swain SM. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014;32(33):3753-61.
166. Wang JX, He YL, Zhu ST, Yang S, and Zhang ST. Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma. World journal of gastroenterology. 2011;17(37):4225-30.
167. Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, Greco C, Feruglio F, Molgora M, Laface I, et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell. 2015;160(4):700-14.
168. Choi B, Lee EJ, Song DH, Yoon SC, Chung YH, Jang Y, Kim SM, Song Y, Kang SW, Yoon SY, et al. Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function. Oncotarget. 2014;5(2):481-92.
169. Chang WC, Wu SL, Huang WC, Hsu JY, Chan SH, Wang JM, Tsai JP, and Chen BK. PTX3 gene activation in EGF-induced head and neck cancer cell metastasis. Oncotarget. 2015;6(10):7741-57.
170. Choi B, Lee EJ, Park YS, Kim SM, Kim EY, Song Y, Kang SW, Rhu MH, and Chang EJ. Pentraxin-3 Silencing Suppresses Gastric Cancer-related Inflammation by Inhibiting Chemotactic Migration of Macrophages. Anticancer research. 2015;35(5):2663-8.
171. Ying TH, Lee CH, Chiou HL, Yang SF, Lin CL, Hung CH, Tsai JP, and Hsieh YH. Knockdown of Pentraxin 3 suppresses tumorigenicity and metastasis of human cervical cancer cells. Scientific reports. 2016;6(29385.
172. Chi JY, Hsiao YW, Li CF, Lo YC, Lin ZY, Hong JY, Liu YM, Han X, Wang SM, Chen BK, et al. Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers. Oncotarget. 2015;6(27):23987-4001.
173. Magrini E, Mantovani A, and Garlanda C. The Dual Complexity of PTX3 in Health and Disease: A Balancing Act? Trends in molecular medicine. 2016;22(6):497-510.
174. Ko CY, Chang LH, Lee YC, Sterneck E, Cheng CP, Chen SH, Huang AM, Tseng JT, and Wang JM. CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells. Neurobiology of aging. 2012;33(2):422.e11-25.
175. Ronca R, Alessi P, Coltrini D, Di Salle E, Giacomini A, Leali D, Corsini M, Belleri M, Tobia C, Garlanda C, et al. Long pentraxin-3 as an epithelial-stromal fibroblast growth factor-targeting inhibitor in prostate cancer. The Journal of pathology. 2013;230(2):228-38.
176. Stallone G, Cormio L, Netti GS, Infante B, Selvaggio O, Fino GD, Ranieri E, Bruno F, Prattichizzo C, Sanguedolce F, et al. Pentraxin 3: a novel biomarker for predicting progression from prostatic inflammation to prostate cancer. Cancer research. 2014;74(16):4230-8.
177. Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S, Pasqualini F, Grosso F, Sanfilippo R, Casali PG, et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer research. 2010;70(6):2235-44.
178. Leali D, Inforzato A, Ronca R, Bianchi R, Belleri M, Coltrini D, Di Salle E, Sironi M, Norata GD, Bottazzi B, et al. Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction: a biological rheostat for fibroblast growth factor 2-mediated angiogenesis. Arteriosclerosis, thrombosis, and vascular biology. 2012;32(3):696-703.