活化的基質為固體腫瘤微環境的特徵，其包含豐富的發炎介質、蛋白水解酶、浸潤的白血球以及失調的微血管組織。然而，人們對於其中詳盡的分子機制與信號通路仍有許多尚未明瞭的部份。近期我們發現腫瘤微環境中的正五聚蛋白3(PTX3)，會抑制白血球的吞噬作用並促進腫瘤轉移及血管新生，在癌症進展中扮演關鍵角色。我們先前的研究已證明抑制PTX3會顯著降低乳癌細胞的遷移、侵襲與幹細胞特徵。為了更好地闡明PTX3於生物學上之意義，我們建立哺乳動物細胞表達的重組蛋白純化系統，並利用高通量西方墨點微陣列方法分析PTX3誘導的下游信號通路。繼發現PTX3的受體(X受體)之後，我們進一步證實PTX3會經由X受體活化乳癌細胞中的RAC1、PAK1、AKT還有 NF-kB p65等蛋白。除此之外，我們亦證明X受體介導由PTX3所誘發的NF-kB信號通路而增加RANKL與MMP2的表現量。值得注意的是，我們也發現PTX3參與幹細胞特徵相關基因TWIST2和NANOG的表現量調節。綜上所述，本研究為PTX3於生物學上之意義及其分子機制提供了新的見解，有助於開發更具潛力的治療策略與抗癌藥物。

The microenvironment of solid tumors is characterized by a reactive stroma containing an abundance of inflammatory mediators, leukocytes, dysregulated vessels and proteolytic enzymes. However, the reasons and detailed molecular mechanisms underlying this remain largely unclear. Recently, we found that Pentraxin 3 (PTX3) plays a crucial pro-tumor role in inhibition of phagocytosis, promotion of metastasis and angiogenesis in tumor microenvironment. Our previous results demonstrated that the inhibition of PTX3 can significantly attenuate the migration, invasion, and stemness of breast cancer cells. To elucidate the PTX3 biology, a eukaryotic recombinant PTX3 protein purification system was established in mammal cells. Moreover, PTX3-induced signaling pathways in breast cancer cells were identified via a Micro-western array analysis. Following the identification of PTX3 receptor (X receptor), the PTX3-induced signaling pathways was further confirmed by loss-of-function assays. We found that RAC1, PAK1, AKT, and NF-kB p65 are responsive to PTX3 through X receptor. In addition, X receptor mediates the PTX3-induced NF-kB signaling to increase the expression of RANKL and MMP2. Notably, PTX3 is also involved in the induction of stemness-related genes TWIST2 and NANOG. In summary, this study provides new insights into the molecular mechanisms of PTX3 biology, and thus contributes to generating a potent therapeutic strategy as well as more specific application for anti-cancer drugs.

1. Morris, C. M., Smith, E., Davies, S., and Wilkinson, L. S. (2006) An audit of women attending for symptomatic recall following routine NHSBSP screening at the South West London Breast Screening Service between 1991 and 2004. Breast Cancer Res 8, S20-S20
2. Mathew, J., and Perez, E. A. (2011) Trastuzumab emtansine in human epidermal growth factor receptor 2-positive breast cancer: a review. Curr Opin Oncol 23, 594-600
3. Jemal, A., Siegel, R., Xu, J. Q., and Ward, E. (2010) Cancer Statistics, 2010. Ca-Cancer J Clin 60, 277-300
4. Tinoco, G., Warsch, S., Gluck, S., Avancha, K., and Montero, A. J. (2013) Treating Breast Cancer in the 21st Century: Emerging Biological Therapies. J Cancer 4, 117-132
5. Greenberg, P. A. C., Hortobagyi, G. N., Smith, T. L., Ziegler, L. D., Frye, D. K., and Buzdar, A. U. (1996) Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14, 2197-2205
6. Sorlie, T., Perou, C. M., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., Thorsen, T., Quist, H., Matese, J. C., Brown, P. O., Botstein, D., Lonning, P. E., and Borresen-Dale, A. L. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. P Natl Acad Sci USA 98, 10869-10874
7. Higgins, M. J., and Baselga, J. (2011) Targeted therapies for breast cancer. The Journal of clinical investigation 121, 3797-3803
8. Santa-Maria, C. A., and Gradishar, W. J. (2015) Changing Treatment Paradigms in Metastatic Breast Cancer: Lessons Learned. JAMA oncology 1, 528-534; quiz 549
9. Scaltriti, M., Eichhorn, P. J., Cortes, J., Prudkin, L., Aura, C., Jimenez, J., Chandarlapaty, S., Serra, V., Prat, A., Ibrahim, Y. H., Guzman, M., Gili, M., Rodriguez, O., Rodriguez, S., Perez, J., Green, S. R., Mai, S., Rosen, N., Hudis, C., and Baselga, J. (2011) Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2(+) breast cancer patients. P Natl Acad Sci USA 108, 3761-3766
10. Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., Beijersbergen, R. L., Mills, G. B., de Vijver, M. J. V., and Bernards, R. (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12, 395-402
11. Hanahan, D., and Weinberg, R. A. (2011) Hallmarks of Cancer: The Next Generation. Cell 144, 646-674
12. Datta, S. R., Brunet, A., and Greenberg, M. E. (1999) Cellular survival: a play in three Akts. Gene Dev 13, 2905-2927
13. Liu, P. X., Cheng, H. L., Roberts, T. M., and Zhao, J. J. (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8, 627-644
14. Tokunaga, E., Kimura, Y., Mashino, K., Oki, E., Kataoka, A., Ohno, S., Morita, M., Kakeji, Y., Baba, H., and Maehara, Y. (2006) Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast cancer 13, 137-144
15. Stal, O., Perez-Tenorio, G., Akerberg, L., Olsson, B., Nordenskjold, B., Skoog, L., and Rutqvist, L. E. (2003) Akt kinases in breast cancer and the results of adjuvant therapy. Breast Cancer Res 5, R37-44
16. Miron, M., Lasko, P., and Sonenberg, N. (2003) Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster. Mol Cell Biol 23, 9117-9126
17. Santen, R. J., Song, R. X., McPherson, R., Kumar, R., Adam, L., Jeng, M. H., and Yue, W. (2002) The role of mitogen-activated protein (MAP) kinase in breast cancer. The Journal of steroid biochemistry and molecular biology 80, 239-256
18. Saini, K. S., Loi, S., de Azambuja, E., Metzger-Filho, O., Saini, M. L., Ignatiadis, M., Dancey, J. E., and Piccart-Gebhart, M. J. (2013) Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev 39, 935-946
19. Giehl, K. (2005) Oncogenic Ras in tumour progression and metastasis. Biological chemistry 386, 193-205
20. Reddy, K. B., Nabha, S. M., and Atanaskova, N. (2003) Role of MAP kinase in tumor progression and invasion. Cancer metastasis reviews 22, 395-403
21. Kennedy, N. J., and Davis, R. J. (2003) Role of JNK in tumor development. Cell cycle 2, 199-201
22. Eferl, R., Ricci, R., Kenner, L., Zenz, R., David, J. P., Rath, M., and Wagner, E. F. (2003) Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 112, 181-192
23. Dunn, K. L., Espino, P. S., Drobic, B., He, S., and Davie, J. R. (2005) The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. Biochemistry and cell biology = Biochimie et biologie cellulaire 83, 1-14
24. Lee, K. S., Shin, J. S., and Nam, K. S. (2013) Starfish polysaccharides downregulate metastatic activity through the MAPK signaling pathway in MCF-7 human breast cancer cells. Molecular biology reports 40, 5959-5966
25. Lai, Y., Liu, X. H., Zeng, Y., Zhang, Y., Shen, Y., and Liu, Y. F. (2012) Interleukin-8 induces the endothelial cell migration through the Rac1/RhoA-p38MAPK pathway. Eur Rev Med Pharmaco 16, 630-638
26. Sander, E. E., and Collard, J. G. (1999) Rho-like GTPases: Their role in epithelial cell-cell adhesion and invasion. Eur J Cancer 35, 1302-1308
27. Vega, F. M., and Ridley, A. J. (2008) Rho GTPases in cancer cell biology. FEBS letters 582, 2093-2101
28. Fritz, G., Brachetti, C., Bahlmann, F., Schmidt, M., and Kaina, B. (2002) Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. British journal of cancer 87, 635-644
29. Salh, B., Marotta, A., Wagey, R., Sayed, M., and Pelech, S. (2002) Dysregulation of phosphatidylinositol 3-kinase and downstream effectors in human breast cancer. International journal of cancer 98, 148-154
30. Takase, O., Yoshikawa, M., Idei, M., Hirahashi, J., Fujita, T., Takato, T., Isagawa, T., Nagae, G., Suemori, H., Aburatani, H., and Hishikawa, K. (2013) The Role of NF-kappa B Signaling in the Maintenance of Pluripotency of Human Induced Pluripotent Stem Cells. Plos One 8
31. Ghosh, S., and Karin, M. (2002) Missing pieces in the NF-kappa B puzzle. Cell 109, S81-S96
32. Sovak, M. A., Bellas, R. E., Kim, D. W., Zanieski, G. J., Rogers, A. E., Traish, A. M., and Sonenshein, G. E. (1997) Aberrant nuclear factor-kappa B/Rel expression and the pathogenesis of breast cancer. Journal of Clinical Investigation 100, 2952-2960
33. Cao, Y. X., Bonizzi, G., Seagroves, T. N., Greten, F. R., Johnson, R., Schmidt, E. V., and Karin, M. (2001) IKK alpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell 107, 763-775
34. Karin, M. (2006) Nuclear factor-kappa B in cancer development and progression. Nature 441, 431-436
35. Basseres, D. S., and Baldwin, A. S. (2006) Nuclear factor-kappa B and inhibitor of kappa B kinase pathways in oncogenic initiation and progression. Oncogene 25, 6817-6830
36. Biswas, D. K., Shi, Q., Baily, S., Strickland, I., Ghosh, S., Pardee, A. B., and Iglehart, J. D. (2004) NF-KB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. P Natl Acad Sci USA 101, 10137-10142
37. Cogswell, P. C., Guttridge, D. C., Funkhouser, W. K., and Baldwin, A. S. (2000) Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. Oncogene 19, 1123-1131
38. Huber, M. A., Azoitei, N., Baumann, B., Grunert, S., Sommer, A., Pehamberger, H., Kraut, N., Beug, H., and Wirth, T. (2004) NF-kappa B is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. Journal of Clinical Investigation 114, 569-581
39. Liu, M., Sakamaki, T., Casimiro, M. C., Willmarth, N. E., Quong, A. A., Ju, X. M., Ojeifo, J., Jiao, X. M., Yeow, W. S., Katiyar, S., Shirley, L. A., Joyce, D., Lisanti, M. P., Albanese, C., and Pestell, R. G. (2010) The Canonical NF-kappa B Pathway Governs Mammary Tumorigenesis in Transgenic Mice and Tumor Stem Cell Expansion. Cancer Res 70, 10464-10473
40. Almeida, L. O., Abrahao, A. C., Rosselli-Murai, L. K., Giudice, F. S., Zagni, C., Leopoldino, A. M., Squarize, C. H., and Castilho, R. M. (2014) NF kappa B mediates cisplatin resistance through histone modifications in head and neck squamous cell carcinoma (HNSCC). Febs Open Bio 4, 96-104
41. Godwin, P., Baird, A. M., Heavey, S., Barr, M. P., O'Byrne, K. J., and Gately, K. (2013) Targeting nuclear factor-kappa B to overcome resistance to chemotherapy. Frontiers in oncology 3, 120
42. Artacho-Cordon, A., Artacho-Cordon, F., Rios-Arrabal, S., Calvente, I., and Nunez, M. I. (2012) Tumor microenvironment and breast cancer progression A complex scenario. Cancer Biol Ther 13, 14-24
43. Kohrmann, A., Kammerer, U., Kapp, M., Dietl, J., and Anacker, J. (2009) Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. Bmc Cancer 9
44. Korkaya, H., Liu, S. L., and Wicha, M. S. (2011) Breast cancer stem cells, cytokine networks, and the tumor microenvironment. Journal of Clinical Investigation 121, 3804-3809
45. Garlanda, C., Bottazzi, B., Bastone, A., and Mantovani, A. (2005) Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 23, 337-366
46. Presta, M., Camozzi, M., Salvatori, G., and Rusnati, M. (2007) Role of the soluble pattern recognition receptor PTX3 in vascular biology. J Cell Mol Med 11, 723-738
47. Bottazzi, B., Vouret-Craviari, V., Bastone, A., De Gioia, L., Matteucci, C., Peri, G., Spreafico, F., Pausa, M., D'Ettorre, C., Gianazza, E., Tagliabue, A., Salmona, M., Tedesco, F., Introna, M., and Mantovani, A. (1997) 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. J Biol Chem 272, 32817-32823
48. Inforzato, A., Reading, P. C., Barbati, E., Bottazzi, B., Garlanda, C., and Mantovani, A. (2013) The "sweet" side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation. Front Immunol 3
49. Alles, V. V., Bottazzi, B., Peri, G., Golay, J., Introna, M., and Mantovani, A. (1994) Inducible Expression of Ptx3, a New Member of the Pentraxin Family, in Human Mononuclear Phagocytes. Blood 84, 3483-3493
50. Lee, G. W., Lee, T. H., and Vilcek, J. (1993) Tsg-14, a Tumor Necrosis Factor-Inducible and Il-1-Inducible Protein, Is a Novel Member of the Pentaxin Family of Acute Phase Proteins. J Immunol 150, 1804-1812
51. Inforzato, A., Peri, G., Doni, A., Garlanda, C., Mantovani, A., Bastone, A., Carpentieri, A., Amoresano, A., Pucci, P., Roos, A., Daha, M. R., Vincenti, S., Gallo, G., Carminati, P., De Santis, R., and Salvatori, G. (2006) Structure and function of the long pentraxin PTX3 glycosidic moiety: Fine-tuning of the interaction with C1q and complement activation. Biochemistry-Us 45, 11540-11551
52. Deban, L., Russo, R. C., Sironi, M., Moalli, F., Scanziani, M., Zambelli, V., Cuccovillo, I., Bastone, A., Gobbi, M., Valentino, S., Doni, A., Garlanda, C., Danese, S., Salvatori, G., Sassano, M., Evangelista, V., Rossi, B., Zenaro, E., Constantin, G., Laudanna, C., Bottazzi, B., and Mantovani, A. (2010) Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol 11, 328-U374
53. Diamandis, E. P., Goodglick, L., Planque, C., and Thomquist, M. D. (2011) Pentraxin-3 Is a Novel Biomarker of Lung Carcinoma. Clin Cancer Res 17, 2395-2399
54. Pavlou, M. P., Dimitromanolakis, A., and Diamandis, E. P. (2013) Coupling proteomics and transcriptomics in the quest of subtype-specific proteins in breast cancer. Proteomics 13, 1083-1095
55. Germano, G., Frapolli, R., Simone, M., Tavecchio, M., Erba, E., Pesce, S., Pasqualini, F., Grosso, F., Sanfilippo, R., Casali, P. G., Gronchi, A., Virdis, E., Tarantino, E., Pilotti, S., Greco, A., Nebuloni, M., Galmarini, C. M., Tercero, J. C., Mantovani, A., D'Incalci, M., and Allavena, P. (2010) Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells. Cancer Res 70, 2235-2244
56. Stallone, G., Cormio, L., Netti, G. S., Infante, B., Selvaggio, O., Di Fino, G., Ranieri, E., Bruno, F., Prattichizzo, C., Sanguedolce, F., Tortorella, S., Bufo, P., Grandaliano, G., and Carrieri, G. (2014) Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer. Cancer Res 74, 4230-4238
57. Locatelli, M., Ferrero, S., Boneschi, F. M., Boiocchi, L., Zavanone, M., Gaini, S. M., Bello, L., Valentino, S., Barbati, E., Nebuloni, M., Mantovani, A., and Garlanda, C. (2013) The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas. J Neuroimmunol 260, 99-106
58. Hsiao, Y. W., Li, C. F., Chi, J. Y., Tseng, J. T., Chang, Y., Hsu, L. J., Lee, C. H., Chang, T. H., Wang, S. M., Wang, D. D. H., Cheng, H. C., and Wang, J. M. (2013) CCAAT/Enhancer Binding Protein delta in Macrophages Contributes to Immunosuppression and Inhibits Phagocytosis in Nasopharyngeal Carcinoma. Sci Signal 6
59. Chang, W. C., Wu, S. L., Huang, W. C., Hsu, J. Y., Chan, S. H., Wang, J. M., Tsai, J. P., and Chen, B. K. (2015) PTX3 gene activation in EGF-induced head and neck cancer cell metastasis. Oncotarget 6, 7741-7757
60. Kondo, S., Ueno, H., Hosoi, H., Hashimoto, J., Morizane, C., Koizumi, F., Tamura, K., and Okusaka, T. (2013) Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma. British journal of cancer 109, 739-746
61. Chi, J. Y., Hsiao, Y. W., Li, C. F., Lo, Y. C., Lin, Z. Y., Hong, J. Y., Liu, Y. M., Han, X., Wang, S. M., Chen, B. K., Tsai, K. K., and Wang, J. M. (2015) Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers. Oncotarget 6, 23987-24001
62. Geback, T., Schulz, M. M. P., Koumoutsakos, P., and Detmar, M. (2009) TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays. Biotechniques 46, 265-+
63. Ciaccio, M. F., Wagner, J. P., Chuu, C. P., Lauffenburger, D. A., and Jones, R. B. (2010) Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nat Methods 7, 148-U195
64. Karin, M., Cao, Y. X., Greten, F. R., and Li, Z. W. (2002) NF-kappa B in cancer: From innocent bystander to major culprit. Nat Rev Cancer 2, 301-310
65. Song, F. N., Duan, M., Liu, L. Z., Wang, Z. C., Shi, J. Y., Yang, L. X., Zhou, J., Fan, J., Gao, Q., and Wang, X. Y. (2014) RANKL Promotes Migration and Invasion of Hepatocellular Carcinoma Cells via NF-kappa B-Mediated Epithelial-Mesenchymal Transition. Plos One 9
66. Lin, M. L., Lu, Y. C., Chung, J. G., Wang, S. G., Lin, H. T., Kang, S. E., Tang, C. H., Ko, J. L., and Chen, S. S. (2010) Down-Regulation of MMP-2 Through the p38 MAPK-NF-kappa B-Dependent Pathway by Aloe-Emodin Leads to Inhibition of Nasopharyngeal Carcinoma Cell Invasion. Mol Carcinogen 49, 783-797
67. Zhao, Y. B., Wang, H. B., Li, X. L., Cao, M. R., Lu, H. L., Meng, Q. W., Pang, H., Li, H. L., Nadolny, C., Dong, X. Q., and Cai, L. (2014) Ang II-AT1R Increases Cell Migration Through PI3K/AKT and NF-kappa B Pathways in Breast Cancer. J Cell Physiol 229, 1855-1862
68. Grivennikov, S. I., Greten, F. R., and Karin, M. (2010) Immunity, Inflammation, and Cancer. Cell 140, 883-899
69. Mantovani, A., Allavena, P., Sica, A., and Balkwill, F. (2008) Cancer-related inflammation. Nature 454, 436-444
70. Mao, Y., Keller, E. T., Garfield, D. H., Shen, K. W., and Wang, J. H. (2013) Stromal cells in tumor microenvironment and breast cancer. Cancer Metast Rev 32, 303-315
71. Choi, B., Lee, E. J., Song, D. H., Yoon, S. C., Chung, Y. H., Jang, Y., Kim, S. M., Song, Y., Kang, S. W., Yoon, S. Y., and Chang, E. J. (2014) Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function. Oncotarget 5, 481-492
72. Cain, J. A., Solis, N., and Cordwell, S. J. (2014) Beyond gene expression: the impact of protein post-translational modifications in bacteria. Journal of proteomics 97, 265-286
73. Zhang, H., An, F., Tang, L., and Qiu, R. G. (2014) Multiple Effects of a Novel Epothilone Analog on Cellular Processes and Signaling Pathways Regulated by Rac1 GTPase in the Human Breast Cancer Cells. Korean J Physiol Pha 18, 109-120
74. Hu, Y. L., Li, S., Miao, H., Tsou, T. C., del Pozo, M. A., and Chien, S. (2002) Roles of microtubule dynamics and small GTPase rac in endothelial cell migration and lamellipodium formation under flow. J Vasc Res 39, 465-476
75. Dunn, K. L., Espino, P. S., Drobic, B., He, S. H., and Davie, J. R. (2005) The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire 83, 1-14
76. Lu, J. H., Marnell, L. L., Marjon, K. D., Mold, C., Du Clos, T. W., and Sun, P. D. (2008) Structural recognition and functional activation of Fc gamma R by innate pentraxins. Nature 456, 989-U986
77. Cassard, L., Cohen-Solal, J., Camilleri-Broet, S., Fournier, E., Fridman, W. H., and Sautes-Fridman, C. (2006) Fc gamma receptors and cancer. Springer Semin Immun 28, 321-328
78. Rose, D. M., Winston, B. W., Chan, E. D., Riches, D. W. H., Gerwins, P., Johnson, G. L., and Henson, P. M. (1997) Fc gamma receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophages - Role for p42(MAPK) in Fc gamma receptor-stimulated TNF-alpha synthesis. J Immunol 158, 3433-3438
79. Lai, K. C., Huang, A. C., Hsu, S. C., Kuo, C. L., Yang, J. S., Wu, S. H., and Chung, J. G. (2010) Benzyl Isothiocyanate (BITC) Inhibits Migration and Invasion of Human Colon Cancer HT29 Cells by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase Plasminogen (uPA) through PKC and MAPK Signaling Pathway. J Agr Food Chem 58, 2935-2942
80. Tung, J. N., Ko, C. P., Yang, S. F., Cheng, C. W., Chen, P. N., Chang, C. Y., Lin, C. L., Yang, T. F., Hsieh, Y. H., and Chen, K. C. (2016) Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo. Journal of neuro-oncology
81. Palafox, M., Ferrer, I., Pellegrini, P., Vila, S., Hernandez-Ortega, S., Urruticoechea, A., Climent, F., Soler, M. T., Munoz, P., Vinals, F., Tometsko, M., Branstetter, D., Dougall, W. C., and Gonzalez-Suarez, E. (2012) RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res 72, 2879-2888
82. Yoneda, T., Tanaka, S., and Hata, K. (2013) Role of RANKL/RANK in primary and secondary breast cancer. World journal of orthopedics 4, 178-185
83. Hu, F. Q., Qiao, T., Xie, X., Hu, R., and Xiao, H. B. (2014) Knockdown of the Inflammatory Factor Pentraxin-3 Suppresses Growth and Invasion of Lung Adenocarcinoma through the Akt and Nf-Kappa B Pathways. J Biol Reg Homeos Ag 28, 649-657
84. Ito, T., Sato, N., Yamaguchi, Y., Tazawa, C., Moriya, T., Hirakawa, H., and Hayashi, S. (2015) Differences in Stemness Properties Associated With the Heterogeneity of Luminal-Type Breast Cancer. Clin Breast Cancer 15, E93-E103
85. Wang, D., Lu, P., Zhang, H., Luo, M. N., Zhang, X., Wei, X. F., Gao, J. Y., Zhao, Z. W., and Liu, C. G. (2014) Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients. Oncotarget 5, 10803-10815
86. Fang, X., Cai, Y., Liu, J., Wang, Z., Wu, Q., Zhang, Z., Yang, C. J., Yuan, L., and Ouyang, G. (2011) Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal. Oncogene 30, 4707-4720