先前的研究顯示，穿膜蛋白質CD133會表現在許多的腫瘤幹細胞中，然而其在生理上所扮演的角色目前仍尚未釐清，因此本實驗室便利用慢病毒載體將人類的CD133基因轉殖到大鼠神經膠質瘤細胞株C6( hCD133+-C6 )，用以模擬腫瘤幹細胞的表現，並以不表現CD133基因之C6-PURO模擬一般的腫瘤細胞。由結果顯示，在有表現人類CD133基因的C6細胞中，其細胞移動及形成群落的能力遠高於不表現的C6-PURO，表示CD133基因的確會影響大鼠神經膠質瘤C6細胞癌化的程度。依據先前的文獻顯示當大鼠的神經膠質瘤生成時，大量的P2X7受器會表現於細胞表面，促使細胞增生，因此本篇進一步利用P2X7受器的拮抗劑oxATP處理C6-PURO及hCD133+-C6之細胞，由結果顯示不論是C6-PURO或hCD133+-C6之細胞都會產生分化的情形且兩者的細胞存活率及群落生長能力均下降，顯示oxATP的確可透過P2X7 受器影響神經膠質瘤之生長。由於過去的文獻發現，當身體處於急性發炎反應下腫瘤會萎縮，因此為了進一步釐清這些發炎因子是如何調控腫瘤細胞，透過給予不同的發炎因子處理發現當以dbcAMP （cAMP類似物）作用時，則可有效抑制C6-PURO及hCD133+-C6細胞的移動，顯示大量表現的dbcAMP或許也同樣是透過抑制P2X7受器之表現，進而使細胞的移動下降。

According to recent studies, the trans-membrane protein CD133 is expressed in many cancer stem cells. However, the role of CD133 remains unclear. In order to know its physiological role, we transfect the lentivirus with or without human CD133 gene to rat glioma cell line C6 (hCD133+-C6 or C6-PURO) to mimic the performance of cancer stem cells or normal tumor cells. The results show that the C6 with the expression of CD133 gene have better cell migration and colony formation than C6-PURO, which means the expression of CD133 affects the tumorigenesis of C6 glioma. Based on previous studies, there are many P2X7 receptors expressing on glioma cell surface to promote cell proliferation, therefore we use the P2X7 antagonist oxATP to treat C6-PURO and hCD133+-C6. After treatment, both C6-PURO and hCD133+-C6 were increased in differentiation but decreased in cell viability and colony formation. These data indicated that oxATP through P2X7 receptor does affect the growth of glioma. When human is in acute inflammation, the tumor may regress. In order to know how inflammatory factor regulating the tumor cell, we use different inflammatory cytokine to glioma. We found that using dbcAMP (cAMP analogue) can effectively inhibit the migration of C6-PURO and hCD133+-C6, which may also through inhibition of expression of P2X7 receptor to reduce the rate of cell migration.

Aggarwal, B. B., S. Shishodia, et al. (2006). "Inflammation and cancer: how hot is the link?" Biochem Pharmacol 72(11): 1605-1621.
Beier, D., P. Hau, et al. (2007). "CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles." Cancer Res 67(9): 4010-4015.
Benda P, Lightbody J, Sato G, Levine L, Sweet W (1968) Differentiated rat glial cell strain in tissue culture. Science 161:370-371
Bjerkvig, R., B. B. Tysnes, et al. (2005). "Opinion: the origin of the cancer stem cell: current controversies and new insights." Nat Rev Cancer 5(11): 899-904.
Calabresi, P., D. L. Dexter, et al. (1979). "Clinical and pharmacological implications of cancer cell differentiation and heterogeneity." Biochem Pharmacol 28(12): 1933-1941.
Chen, T. C., D. R. Hinton, et al. (1998). "Up-regulation of the cAMP/PKA pathway inhibits proliferation, induces differentiation, and leads to apoptosis in malignant gliomas." Lab Invest 78(2): 165-174.
Combs, S. E., V. Widmer, et al. (2005). "Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM)." Cancer 104(10): 2168-2173.
Coussens, L. M. and Z. Werb (2002). "Inflammation and cancer." Nature 420(6917): 860-867.
Eigenthaler, M., C. Nolte, et al. (1992). "Concentration and regulation of cyclic nucleotides, cyclic-nucleotide-dependent protein kinases and one of their major substrates in human platelets. Estimating the rate of cAMP-regulated and cGMP-regulated protein phosphorylation in intact cells." Eur J Biochem 205(2): 471-481.
Fang, K. M., Y. L. Wang, et al. (2011). "Expression of macrophage inflammatory protein-1alpha and monocyte chemoattractant protein-1 in glioma-infiltrating microglia: involvement of ATP and P2X receptor." J Neurosci Res 89(2): 199-211.
Fan, X., L. Khaki, et al. (2010). "NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts." Stem Cells 28(1): 5-16.
Furman, M. A. and K. Shulman (1977). "Cyclic AMP and adenyl cyclase in brain tumors." J Neurosurg 46(4): 477-483.
Gadji, M., A. M. Crous, et al. (2009). "EGF receptor inhibitors in the treatment of glioblastoma multiform: old clinical allies and newly emerging therapeutic concepts." Eur J Pharmacol 625(1-3): 23-30.
Grivennikov, S. I., F. R. Greten, et al. (2010). "Immunity, inflammation, and cancer." Cell 140(6): 883-899.
Hegi, M. E., A. C. Diserens, et al. (2005). "MGMT gene silencing and benefit from temozolomide in glioblastoma." N Engl J Med 352(10): 997-1003.
Hoffman, L. M., S. E. Brooks, et al. (1994). "Cyclic AMP causes differentiation and decreases the expression of neutral glycosphingolipids in cell cultures derived from a malignant glioma." Biochim Biophys Acta 1222(1): 37-44.
Horst, D., S. K. Scheel, et al. (2009). "The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer." J Pathol 219(4): 427-434.
Huang, Z., L. Cheng, et al. (2010). "Cancer stem cells in glioblastoma--molecular signaling and therapeutic targeting." Protein Cell 1(7): 638-655.
Humphreys, B. D. and G. R. Dubyak (1998). "Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes." J Leukoc Biol 64(2): 265-273.
Hu, Y. Y., M. H. Zheng, et al. (2011). "Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells." BMC Cancer 11: 82.
Lai CP, Bechberger JF, Thompson RJ, MacVicar BA, Bruzzone R, Naus CC (2007) Tumor-suppressive effects of pannexin 1 in C6 glioma cells. Cancer Res 67:1545-1554.
Li, J., Y. Cui, et al. (2011). "Notch1 is an independent prognostic factor for patients with glioma." J Surg Oncol 103(8): 813-817.
Lottaz, C., D. Beier, et al. (2010). "Transcriptional profiles of CD133+ and CD133- glioblastoma-derived cancer stem cell lines suggest different cells of origin." Cancer Res 70(5): 2030-2040.
Louis, D. N., H. Ohgaki, et al. (2007). "The 2007 WHO classification of tumours of the central nervous system." Acta Neuropathol 114(2): 97-109.
Lu, X., S. V. Baudouin, et al. (2007). "A comparison of CFU-GM, BFU-E and endothelial progenitor cells using ex vivo expansion of selected cord blood CD133(+) and CD34(+) cells." Cytotherapy 9(3): 292-300.
Maeda, S., H. Shinchi, et al. (2008). "CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer." Br J Cancer 98(8): 1389-1397.
Muller, W., D. Afra, et al. (1977). "Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with astrocytomas." Acta Neurochir (Wien) 37(1-2): 75-91.
Nakazato, Y. (2008). "[The 4th Edition of WHO Classification of Tumours of the Central Nervous System published in 2007]." No Shinkei Geka 36(6): 473-491.
Nguyen, G. H., M. M. Murph, et al. (2011). "Cancer Stem Cell Radioresistance and Enrichment: Where Frontline Radiation Therapy May Fail in Lung and Esophageal Cancers." Cancers (Basel) 3(1): 1232-1252.
Pollak, L., R. Gur, et al. (1997). "Clinical determinants of long-term survival in patients with glioblastoma multiforme." Tumori 83(2): 613-617.
Raghavan, R., P. V. Steart, et al. (1990). "Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study." Neuropathol Appl Neurobiol 16(2): 123-133.
Reya, T., S. J. Morrison, et al. (2001). "Stem cells, cancer, and cancer stem cells." Nature 414(6859): 105-111.
Shmelkov, S. V., J. M. Butler, et al. (2008). "CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors." J Clin Invest 118(6): 2111-2120.
Tang, C., B. T. Ang, et al. (2007). "Cancer stem cell: target for anti-cancer therapy." FASEB J 21(14): 3777-3785.
Takanaga, H., T. Yoshitake, et al. (2004). "cAMP-induced astrocytic differentiation of C6 glioma cells is mediated by autocrine interleukin-6." J Biol Chem 279(15): 15441-15447.
Taylor, L. P. (2010). "Diagnosis, treatment, and prognosis of glioma: five new things." Neurology 75(18 Suppl 1): S28-32.
Walid, M. S., H. F. Smisson, 3rd, et al. (2008). "Long-term survival after glioblastoma multiforme." South Med J 101(9): 971-972.
Walker, D. G. and A. H. Kaye (2001). "Diagnosis and management of astrocytomas, oligodendrogliomas and mixed gliomas: a review." Australas Radiol 45(4): 472-482.
Wei, W., J. K. Ryu, et al. (2008). "Expression and function of the P2X(7) receptor in rat C6 glioma cells." Cancer Lett 260(1-2): 79-87.
Weiss, L. (2000). "Cancer Cell Heterogeneity." Cancer and Metastasis Reviews 19(3): 345-350.
Yang, H. H., M. H. Ma, et al. (2003). "Overcoming drug resistance in multiple myeloma: the emergence of therapeutic approaches to induce apoptosis." J Clin Oncol 21(22): 4239-4247.
Zeppernick, F., R. Ahmadi, et al. (2008). "Stem cell marker CD133 affects clinical outcome in glioma patients." Clin Cancer Res 14(1): 123-129.
Zhen, Y., S. Zhao, et al. (2010). "Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas." Cancer Lett 292(1): 64-72.