請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63848完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山 | |
| dc.contributor.author | Chia-Ju Yang | en |
| dc.contributor.author | 楊佳儒 | zh_TW |
| dc.date.accessioned | 2021-06-16T17:20:47Z | - |
| dc.date.available | 2017-09-18 | |
| dc.date.copyright | 2012-09-18 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-17 | |
| dc.identifier.citation | 1. Lo, W.L., et al. Outcomes of oral squamous cell carcinoma in Taiwan after surgical therapy: factors affecting survival. J Oral Maxillofac Surg 61, 751-758 (2003).
2. Tsuda, M. et al. Oral Cancer. in Functional Biomarkers of Oral Cancer (ed. Ogbureke, K.U.E.) (InTech, 2012). 3. Day, G.L., et al. Second primary tumors in patients with oral cancer. Cancer 70, 14-19 (1992). 4. Chen, M.C., et al. Second primary esophageal or lung cancer in patients with head and neck carcinoma in Taiwan: incidence and risk in relation to primary index tumor site. J Cancer Res Clin Oncol 137, 115-123 (2011). 5. Daftary, D.K., et al. In Oral Diseases in the Tropics (Oxford University, 1992). 6. Boring, C.C., Squires, T.S., Tong, T. & Montgomery, S. Cancer statistics, 1994. CA Cancer J Clin 44, 7-26 (1994). 7. Lumerman, H., et al. Oral epithelial dysplasia and the development of invasive squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79, 321-329 (1995). 8. Lissowska, J., et al. Smoking, alcohol, diet, dentition and sexual practices in the epidemiology of oral cancer in Poland. Eur J Cancer Prev 12, 25-33 (2003). 9. Liu, C.M., et al. Impact of interleukin-8 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan. Oral Dis 18, 307-314 (2012). 10. Hooper, S.J., et al. A molecular analysis of the bacteria present within oral squamous cell carcinoma. J Med Microbiol 56, 1651-1659 (2007). 11. Mager, D.L., et al. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med 3, 27 (2005). 12. Chocolatewala, N., et al. The role of bacteria in oral cancer. Indian J Med Paediatr Oncol 31, 126-131 (2010). 13. Nagy, K.N., et al. Nagy, E. & Newman, H.N. The microflora associated with human oral carcinomas. Oral Oncol 34, 304-308 (1998). 14. Sato, Y., et al. Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment. Cancer Microenviron 2 Suppl 1, 205-214 (2009). 15. Ng, L.K., et al. Toll-like receptor 2 is present in the microenvironment of oral squamous cell carcinoma. Br J Cancer 104, 460-463 (2011). 16. Wang, R.F., et al. Toll-like receptors and immune regulation: implications for cancer therapy. Oncogene 27, 181-189 (2008). 17. Kumagai, Y., et al. Pathogen recognition by innate receptors. J Infect Chemother 14, 86-92 (2008). 18. Szczepanski, M., et al. Assessment of expression of toll-like receptors 2, 3 and 4 in laryngeal carcinoma. Eur Arch Otorhinolaryngol 264, 525-530 (2007). 19. Szczepanski, M.J., et al. Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack. Cancer Res 69, 3105-3113 (2009). 20. Ara, T., et al. Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease. J Periodontal Res 44, 21-27 (2009). 21. Mahanonda, R., et al. IL-8 and IDO expression by human gingival fibroblasts via TLRs. J Immunol 178, 1151-1157 (2007). 22. Tabeta, K., et al. Toll-like receptors confer responsiveness to lipopoly -saccharide from Porphyromonas gingivalis in human gingival fibroblasts. Infect Immun 68, 3731-3735 (2000). 23. Colella, S., et al. Molecular signatures of metastasis in head and neck cancer. Head Neck 30, 1273-1283 (2008). 24. Liu, Z., et al. Integrating multiple microarray datasets on oral squamous cell carcinoma to reveal dysregulated networks. Head Neck (2011). 25. Rao, S.K., et al. Pro-inflammatory genes as biomarkers and therapeutic targets in oral squamous cell carcinoma. J Biol Chem 285, 32512-32521 (2010). 26. Ye, H., et al. Transcriptomic dissection of tongue squamous cell carcinoma. BMC Genomics 9, 69 (2008). 27. Mantovani, A. Cancer: Inflaming metastasis. Nature 457, 36-37 (2009). 28. Rubin, J.B. Chemokine signaling in cancer: one hump or two? Semin Cancer Biol 19, 116-122 (2009). 29. Mucke, T., et al. The role of tumor invasion into the mandible of oral squamous cell carcinoma. J Cancer Res Clin Oncol 137, 165-171 (2011). 30. Neiva, K.G., et al. Cross talk initiated by endothelial cells enhances migration and inhibits anoikis of squamous cell carcinoma cells through STAT3/Akt/ERK signaling. Neoplasia 11, 583-593 (2009). 31. Mulligan, J.K., et al. Secretion of vascular endothelial growth factor by oral squamous cell carcinoma cells skews endothelial cells to suppress T-cell functions. Hum Immunol 70, 375-382 (2009). 32. Wu, R.Q., et al. Novel molecular events in oral carcinogenesis via integrative approaches. J Dent Res 90, 561-572 (2011). 33. Ben-Baruch, A. Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol 16, 38-52 (2006). 34. Witz, I.P. Yin-yang activities and vicious cycles in the tumor microenvironment. Cancer Res 68, 9-13 (2008). 35. Mueller, M.M. & Fusenig, N.E. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4, 839-849 (2004). 36. Werner, S. & Grose, R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 83, 835-870 (2003). 37. Coussens, L.M. & Werb, Z. Inflammation and cancer. Nature 420, 860-867 (2002). 38. De Wever, O. & Mareel, M. Role of tissue stroma in cancer cell invasion. J Pathol 200, 429-447 (2003). 39. Tse, J.C. & Kalluri, R. Mechanisms of metastasis: epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem 101, 816-829 (2007). 40. Sugimoto, H., et al. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 5, 1640-1646 (2006). 41. Kalluri, R. & Zeisberg, M. Fibroblasts in cancer. Nat Rev Cancer 6, 392-401 (2006). 42. Coppe, J.P., et al. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5, 99-118 (2010). 43. Kankuri, E., et al. Fibroblast nemosis arrests growth and induces differentiation of human leukemia cells. Int J Cancer 122, 1243-1252 (2008). 44. Cirri, P. & Chiarugi, P. Cancer associated fibroblasts: the dark side of the coin. Am J Cancer Res 1, 482-497 (2011). 45. de Visser, K.E., et al. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6, 24-37 (2006). 46. Xouri, G. & Christian, S. Origin and function of tumor stroma fibroblasts. Semin Cell Dev Biol 21, 40-46 (2010). 47. Kelly, T. Fibroblast activation protein-alpha and dipeptidyl peptidase IV (CD26): cell-surface proteases that activate cell signaling and are potential targets for cancer therapy. Drug Resist Updat 8, 51-58 (2005). 48. Erez, N., et al. Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer Cell 17, 135-147 (2010). 49. Vaheri, A., et al. Nemosis, a novel way of fibroblast activation, in inflammation and cancer. Exp Cell Res 315, 1633-1638 (2009). 50. Bizik, J., et al. Cell-cell contacts trigger programmed necrosis and induce cyclooxygenase-2 expression. Cell Death Differ 11, 183-195 (2004). 51. Kankuri, E., et al. Induction of hepatocyte growth factor/scatter factor by fibroblast clustering directly promotes tumor cell invasiveness. Cancer Res 65, 9914-9922 (2005). 52. Rasanen, K., et al. Nemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by malignant HaCaT cells. Mol Oncol 2, 340-348 (2008). 53. Jung, D.W., et al. Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7. Int J Cancer 127, 332-344 (2010). 54. Domeij, H., et al. Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival fibroblasts. Eur J Oral Sci 110, 302-306 (2002). 55. Stott-Miller, M., et al. Tumor and salivary matrix metalloproteinase levels are strong diagnostic markers of oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 20, 2628-2636 (2011). 56. Sobral, L.M., et al. Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol 47, 840-846 (2011). 57. Lacina, L., et al. Marker profiling of normal keratinocytes identifies the stroma from squamous cell carcinoma of the oral cavity as a modulatory microenvironment in co-culture. Int J Radiat Biol 83, 837-848 (2007). 58. Wu, M.H., et al. Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res 17, 1306-1316 (2011). 59. Chuang, J.Y., et al. CCL5/CCR5 axis promotes the motility of human oral cancer cells. J Cell Physiol 220, 418-426 (2009). 60. Kupferman, M.E., et al. TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma. Oncogene 29, 2047-2059 (2010). 61. Rasanen, K., et al. A. Differences in the nemosis response of normal and cancer-associated fibroblasts from patients with oral squamous cell carcinoma. PLoS ONE 4, e6879 (2009). 62. Dudas, J., et al. Fibroblasts produce brain-derived neurotrophic factor and induce mesenchymal transition of oral tumor cells. Oral Oncol 47, 98-103 (2011). 63. Ryott, M., et al. Cyclooxygenase-2 expression in oral tongue squamous cell carcinoma. J Oral Pathol Med 40, 385-389 (2011). 64. Giannoni, E., et al. Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal 14, 2361-2371 (2011). 65. Smith, W.L., et al. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69, 145-182 (2000). 66. Greenhough, A., et al. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30, 377-386 (2009). 67. Wang, D. & Dubois, R.N. Prostaglandins and cancer. Gut 55, 115-122 (2006). 68. Alcolea, S., et al. Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2. J Lipid Res 53, 630-642 (2012). 69. Charo, I.F. & Ransohoff, R.M. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354, 610-621 (2006). 70. Rhodus, N.L., et al. NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev 29, 42-45 (2005). 71. Shintani, S., et al. Growth-regulated oncogene-1 expression is associated with angiogenesis and lymph node metastasis in human oral cancer. Oncology 66, 316-322 (2004). 72. Watanabe, H., et al. Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines. Oral Oncol 38, 670-679 (2002). 73. Inoue, K., et al. Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer. Clin Cancer Res 6, 2104-2119 (2000). 74. Daly, A.J., et al. Regulation of HGF and SDF-1 expression by oral fibroblasts--implications for invasion of oral cancer. Oral Oncol 44, 646-651 (2008). 75. Oliveira-Neto, H.H., et al. Involvement of CXCL12 and CXCR4 in lymph node metastases and development of oral squamous cell carcinomas. Tumour Biol 29, 262-271 (2008). 76. Xia, J., et al. Expressions of CXCL12/CXCR4 in oral premalignant and malignant lesions. Mediators Inflamm 2012, 516395 (2012). 77. Kakinuma, T. & Hwang, S.T. Chemokines, chemokine receptors, and cancer metastasis. J Leukoc Biol 79, 639-651 (2006). 78. Wang, D., et al. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med 203, 941-951 (2006). 79. Romanini, J., et al. The role of CXCR2 chemokine receptors in the oral squamous cell carcinoma. Invest New Drugs 30, 1371-1378 (2012). 80. Yang, G., et al. CXCR2 promotes ovarian cancer growth through dysregulated cell cycle, diminished apoptosis, and enhanced angiogenesis. Clin Cancer Res 16, 3875-3886 (2010). 81. Bolitho, C., et al. The chemokine CXCL1 induces proliferation in epithelial ovarian cancer cells by transactivation of the epidermal growth factor receptor. Endocr Relat Cancer 17, 929-940 (2010). 82. Kawanishi, H., et al. Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer. Clin Cancer Res 14, 2579-2587 (2008). 83. Warner, K.A., et al. Endothelial cells enhance tumor cell invasion through a crosstalk mediated by CXC chemokine signaling. Neoplasia 10, 131-139 (2008). 84. Yamada, T., et al. RANKL expression specifically observed in vivo promotes epithelial mesenchymal transition and tumor progression. Am J Pathol 178, 2845-2856 (2011). 85. Deyama, Y., et al. Oral squamous cell carcinomas stimulate osteoclast differentiation. Oncol Rep 20, 663-668 (2008). 86. Qiao, B., et al. Epithelial-mesenchymal transition in oral squamous cell carcinoma triggered by transforming growth factor-beta1 is Snail family-dependent and correlates with matrix metalloproteinase-2 and -9 expressions. Int J Oncol 37, 663-668 (2010). 87. Chambers, T.J. Regulation of the differentiation and function of osteoclasts. J Pathol 192, 4-13 (2000). 88. Boyle, W.J., et al. Osteoclast differentiation and activation. Nature 423, 337-342 (2003). 89. Yamaguchi, M. RANK/RANKL/OPG during orthodontic tooth movement. Orthod Craniofac Res 12, 113-119 (2009). 90. Quan, J., et al. Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms. Cancer Metastasis Rev 31, 209-219 (2012). 91. Jimi, E., et al. The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma. Oral Dis 17, 462-468 (2011). 92. Guise, T.A. & Mundy, G.R. Cancer and bone. Endocr Rev 19, 18-54 (1998). 93. Kayamori, K., et al. Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast formation associated with oral cancers: significance of interleukin-6 synthesized by stromal cells in response to cancer cells. Am J Pathol 176, 968-980 (2010). 94. Liu, X.H., et al. Cross-talk between the interleukin-6 and prostaglandin E(2) signaling systems results in enhancement of osteoclastogenesis through effects on the osteoprotegerin/receptor activator of nuclear factor-{kappa}B (RANK) ligand/RANK system. Endocrinology 146, 1991-1998 (2005). 95. Bonfil, R.D., et al. Proteases, growth factors, chemokines, and the microenvironment in prostate cancer bone metastasis. Urol Oncol 25, 407-411 (2007). 96. Tang, C.H., et al. Bone-derived SDF-1 stimulates IL-6 release via CXCR4, ERK and NF-kappaB pathways and promotes osteoclastogenesis in human oral cancer cells. Carcinogenesis 29, 1483-1492 (2008). 97. Pandruvada, S.N., et al. Role of CXC chemokine ligand 13 in oral squamous cell carcinoma associated osteolysis in athymic mice. Int J Cancer 126, 2319-2329 (2010). 98. Lau, Y.S., et al. RANKL-dependent and RANKL-independent mechanisms of macrophage-osteoclast differentiation in breast cancer. Breast Cancer Res Treat 105, 7-16 (2007). 99. Brown, J.M., et al. Osteoprotegerin and rank ligand expression in prostate cancer. Urology 57, 611-616 (2001). 100. Shin, M., et al. The inhibition of RANKL/RANK signaling by osteoprotegerin suppresses bone invasion by oral squamous cell carcinoma cells. Carcinogenesis 32, 1634-1640 (2011). 101. Okamoto, M., et al. Mechanism for bone invasion of oral cancer cells mediated by interleukin-6 in vitro and in vivo. Cancer 89, 1966-1975 (2000). 102. Tada, T., et al. Oral squamous cell carcinoma cells modulate osteoclast function by RANKL-dependent and -independent mechanisms. Cancer Lett 274, 126-131 (2009). 103. Papadimitrakopoulou, V.A., et al. The prognostic role of loss of insulin-like growth factor-binding protein-3 expression in head and neck carcinogenesis. Cancer Lett 239, 136-143 (2006). 104. Goda, T., et al. Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-beta signalling pathway. Anticancer Res 30, 2615-2623 (2010). 105. Chomczynski, P. & Sacchi, N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc 1, 581-585 (2006). 106. Waugh, D.J. & Wilson, C. The interleukin-8 pathway in cancer. Clin Cancer Res 14, 6735-6741 (2008). 107. Harris, R.E. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 17, 55-67 (2009). 108. Sahin, M., Sahin, E. & Gumuslu, S. Cyclooxygenase-2 in cancer and angiogenesis. Angiology 60, 242-253 (2009). 109. White, J.R., et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem 273, 10095-10098 (1998). 110. Catusse, J., Liotard, A., Loillier, B., Pruneau, D. & Paquet, J.L. Characterization of the molecular interactions of interleukin-8 (CXCL8), growth related oncogen alpha (CXCL1) and a non-peptide antagonist (SB 225002) with the human CXCR2. Biochem Pharmacol 65, 813-821 (2003). 111. Cheng, W.L., et al. Overexpression of CXCL1 and its receptor CXCR2 promote tumor invasion in gastric cancer. Ann Oncol 22, 2267-2276 (2011). 112. Wang, D., et al. MGSA/GRO-mediated melanocyte transformation involves induction of Ras expression. Oncogene 19, 4647-4659 (2000). 113. Nishizawa, M., et al. Oral administration of (11E)-13-oxo-15,16-dinorlabda-8 (20),11-dien-19-oic acid strongly reduces photocarcinogenesis in mouse skin exposed to UV-B irradiation. Chem Biodivers 4, 1003-1007 (2007). 114. Ao, M., et al. Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic epithelium. Cancer Res 67, 4244-4253 (2007). 115. Tsellou, E. & Kiaris, H. Fibroblast independency in tumors: implications in cancer therapy. Future Oncol 4, 427-432 (2008). 116. Rudnick, J.A., et al. Functional heterogeneity of breast fibroblasts is defined by a prostaglandin secretory phenotype that promotes expansion of cancer-stem like cells. PLoS ONE 6, e24605 (2011). 117. Hembruff, S.L. & Cheng, N. Chemokine signaling in cancer: Implications on the tumor microenvironment and therapeutic targeting. Cancer Ther 7, 254-267 (2009). 118. Wislez, M., et al. High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial neoplasia induced by oncogenic kras. Cancer Res 66, 4198-4207 (2006). 119. Bachmeier, B.E., et al. Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis 29, 779-789 (2008). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63848 | - |
| dc.description.abstract | 口腔癌在台灣高居國人癌症死因第六位，在男性中癌症致死率更高居第四；口腔癌具有高度侵犯轉移的能力，下頷骨的破壞發生常被作為判斷鱗狀細胞癌的惡性程度和預後。在腫瘤惡化的過程中，癌症細胞和間質細胞的交互作用扮演重要角色。近年來，各項研究已經逐漸了解癌細胞與癌症相關纖維母細胞之間的關係，其中纖維母細胞的活化狀態會影響腫瘤相關發炎反應的調控。本研究的主軸為觀察人類鱗狀上皮細胞癌與癌症相關纖維母細胞之交互作用。目前已知癌細胞藉由分泌因子促進腫瘤惡化；然而，纖維母細胞表現調控癌症進程的因子仍然不清楚。白血球趨化激素CXCL1可以促進乳癌以及大腸直腸癌的轉移並且會在活化的纖維母細胞中表現，因此，我們假設CXCL1可以在口腔癌之癌相關纖維母細胞中表現並促進口腔癌轉移。分析人類纖維母細胞與癌症相關纖維母細胞的特性中，顯示α-smooth muscle actin 以及發炎相關細胞激素IL-6, IL-8, MCP-1，在癌症相關纖維母細胞的表現量大於正常纖維母細胞，並且癌症相關纖維母細胞促進口腔癌細胞移行的能力比正常纖維母細胞顯著。藉由CXCL1的中和抗體以及其接受器CXCR2的拮抗劑處理，發現CXCL1在纖維母細胞促進的癌細胞移行扮演重要的角色。我們也進一步發現由CXCL1重組蛋白刺激的癌細胞會增加基質金屬蛋白酵素 (matrix metalloproteinase)-2 (MMP-2)的mRNA表現量，但不影響 MMP-1。另ㄧ方面，口腔癌細胞及口腔癌相關纖維母細胞的分泌因子，可以促進老鼠巨噬細胞產生蝕骨細胞分化所需之轉錄因子NFATc1。這些研究結果指出正常纖維母細胞受癌細胞刺激後會表現出癌症相關纖維母細胞的特性，包含發炎相關細胞激素表現與促進癌細胞移行能力。纖維母細胞藉由分泌因子CXCL1調控口腔癌惡化，而經由癌細胞活化的纖維母細胞會增加CXCL1表現量；並且，口腔癌細胞的分泌因子具有促進蝕骨細胞分化的潛力，進一步促進腫瘤生長之發炎行為環境。 | zh_TW |
| dc.description.abstract | Oral squamous cell carcinoma (OSCC), is the fourth common male cancer and the sixth leading cause of cancer death in Taiwan known for its potent activity in local bone invasion/osteolysis, which has a critical influence on the prognosis. Interaction between tumor and stroma cells are important in tumor progression. The effect of tumor cell-secreted factor on metastasis is well established, however little is known about the effect of factors secreted by CAFs on tumor progression. CXCL1, the chemokine involved in promoting of colorectal cancer migration, and can be expressed in activated fibroblast. Therefore, we hypothesis that CXCL1 can be expressed in OSCC-related CAFs and promote tumor migration. Fibroblast activation marker α-smooth muscle actin and proinflammatory cytokine including IL-6, IL-8 and MCP-1 are highly expressed in CAFs than normal gingival fibroblast. The migration of OSCC was enhanced by secreted factors from resting or activated CAFs and inhibited by CXCL1 neutralizing antibody and CXCR2 antagonist SB225002. Moreover, matrix metalloproteinase (MMP)-2 mRNA, but not MMP-1 was elevated in SAS cells in response to CXCL1. On the other hand, the osteoclastogenic factor nuclear factor of activated T-cells c1 can be induced by OSCC or CAFs secreted factors in Raw 264.7 cells. Taken together, CAFs can release some factors including CXCL1 to modulate the tumor migration and osteoclast differentiation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T17:20:47Z (GMT). No. of bitstreams: 1 ntu-101-R99449008-1.pdf: 2775626 bytes, checksum: 4a92dc676f2788603faa627ed121d197 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口試委員審定書 I
Acknowledgement II Abstract in Chinese III Abstract in English IV Abbreviations List V Table of contents VII Chapter 1: Introduction 1 1.1 Oral cancer 1 1.1.1 Epidemiology and Pathology 1 1.1.2 Microorganisms associated with oral cancers 3 1.1.3 Dysregulated network in oral squamous cell carcinoma 5 1.2 Tumor microenvironment 5 1.2.1 Cancer-associated fibroblasts 6 1.2.2 Interactions between tumor and stromal cells of OSCC 9 1.3 Chemokine expression in OSCC 11 1.4 Bone invasion in OSCC 13 Chapter 2: Hypothesis and specific aims 17 Chapter 3: Materials and Methods 18 Chapter 5: Discussion 41 Chapter 6: Reference 46 Chapter 8: Figures 54 Figure 1. Characterization of normal gingival and cancer-associated fibroblasts. 55 Figure 2. Expression of myofibroblast marker α-SMA in normal and cancer associated fibroblasts. 56 Figure 3. Cytokines and chemokines transcription and expression in un-stimulated and CM-stimulated fibroblasts 57 Figure 4. The expression of fibroblast activated protein, hepatocyte growth factor, an COX-2 in gingival and cancer associated fibroblasts. 58 Figure 5. The expression of cox-2 and cxcl1 in fibroblasts; and the correlation of cox-2 between hgf, cxcl1, il-6 and il-8. 59 Figure 6. Un-stimulated fibroblasts condition medium promoted SAS migration ability. 60 Figure 7. Stimulated fibroblasts condition medium enhanced SAS migration 61 Figure 8. The expression of cxcl1 in SAS upregulated by fibroblasts condition medium. 62 Figure 9. The transcription and secretion of CXCL1 in gingival and cancer associated fibroblasts. 63 Figure 10. Effects of neutralized antibodies and inhibitor in SAS migration. 64 Figure 11. CXCL1 induced SAS migration in a dose-dependent manner 65 Figure 12. Inhibition of CXCL1 induced SAS migration by CXCL1 antagonist 66 Figure 13. Fibroblasts condition medium promoted CXCL1 secretion in SAS 67 Figure 14. CXCL1 induced SAS expression of metastasis related gene 68 Figure 15. Characterization of the osteoclastogenic potential of OSCC condition medium. 69 Chapter 7 : Tables and Appendix 70 Table 1. Cancer-Associated Fibroblasts Included in This Study 70 Table 2. Gingival Fibroblasts Included in This Study 71 Appendix 1 72 Appendix 2 73 Appendix 3 74 | |
| dc.language.iso | en | |
| dc.title | 人類鱗狀上皮細胞癌與癌症相關纖維母細胞之交互作用 | zh_TW |
| dc.title | Interactions of oral squamous cell carcinoma and cancer-associated fibroblasts | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許秉寧,張正琪 | |
| dc.subject.keyword | 口腔癌,癌症相關纖維母細胞,白血球趨化激素,蝕骨作用,癌症轉移, | zh_TW |
| dc.subject.keyword | Oral squamous cell carcinoma,Cancer-associated fibroblast,CXCL1,Osteoclastogenesis,Tumor progression, | en |
| dc.relation.page | 74 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf 目前未授權公開取用 | 2.71 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。