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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李心予(Hsinyu Lee) | |
dc.contributor.author | Chuan-En Lin | en |
dc.contributor.author | 林傳恩 | zh_TW |
dc.date.accessioned | 2021-06-13T07:01:55Z | - |
dc.date.available | 2014-08-22 | |
dc.date.copyright | 2011-08-22 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-20 | |
dc.identifier.citation | REFERENCE
1. Arya, M., et al., The metastatic cascade in prostate cancer. Surgical Oncology-Oxford, 2006. 15(3): p. 117-128. 2. Dale Rex Coman, M.D., Decreased Mutual Adhesiveness, a Property of Cells from Squamous Cell Carcinomas. Cancer Research, 1944. 3. Bussemakers, M.J.G., et al., Complex cadherin expression in human prostate cancer cells. International Journal of Cancer, 2000. 85(3): p. 446-450. 4. Day, M.L., et al., E-cadherin mediates aggregation-dependent survival of prostate and mammary epithelial cells through the retinoblastoma cell cycle control pathway. Journal of Biological Chemistry, 1999. 274(14): p. 9656-9664. 5. Tran, N.L., et al., N-cadherin expression in human prostate carcinoma cell lines - An epithelial-mesenchymal transformation mediating adhesion with stromal cells. American Journal of Pathology, 1999. 155(3): p. 787-798. 6. Bryden, A.A.G., et al., E-cadherin and beta-catenin are down-regulated in prostatic bone metastases. Bju International, 2002. 89(4): p. 400-403. 7. Nagakawa, O., et al., Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines. Cancer Letters, 2000. 155(2): p. 173-179. 8. Vartanian, R.K. and N. Weidner, Endothelial cell proliferation in prostatic carcinoma and prostatic hyperplasia: Correlation with Gleason's score, microvessel density, and epithelial cell proliferation. Laboratory Investigation, 1995. 73(6): p. 844-850. 9. Brawer MK, D.R., Brown M, et al., Predictors of pathlogic stage in prostatic carcinoma. Cancer 1994. 73: p. 678-687. 10. Bostwick, D.G., et al., Optimized microvessel density analysis improves prediction of cancer stage from prostate needle biopsies. Urology, 1996. 48(1): p. 47-57. 11. Su, J.L., et al., The role of the VEGF-C/VEGFR-3 axis in cancer progression. British Journal of Cancer, 2007. 96(4): p. 541-545. 12. Zeng, Y.P., et al., Lymphatic vessel density and lymph node metastasis in prostate cancer. Prostate, 2005. 65(3): p. 222-230. 13. Zeng, Y.P., et al., Expression of vascular endothelial growth factor receptor-3 by lymphatic endothelial cells is associated with lymph node metastasis in prostate cancer. Clinical Cancer Research, 2004. 10(15): p. 5137-5144. 14. Brakenhielm, E., et al., Modulating metastasis by a lymphangiogenic switch in prostate cancer. International Journal of Cancer, 2007. 121: p. 2153-2161. 15. Burton, J.B., et al., Suppression of prostate cancer nodal and systemic metastasis by blockade of the lymphangiogenic axis. Cancer Research, 2008. 68(19): p. 7828-7837. 16. Choi, J.W., et al., LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol, 2010. 50: p. 157-86. 17. Noguchi, K., et al., Lysophosphatidic acid (LPA) and its receptors. Curr Opin Pharmacol, 2009. 9(1): p. 15-23. 18. Liu, S., et al., ATX-LPA receptor axis in inflammation and cancer. Cell Cycle, 2009. 8(22): p. 3695-701. 19. Liu, S.Y., et al., Expression of Autotaxin and Lysophosphatidic Acid Receptors Increases Mammary Tumorigenesis, Invasion, and Metastases. Cancer Cell, 2009. 15(6): p. 539-550. 20. Hao, F., et al., Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38 alpha. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids, 2007. 1771(7): p. 883-892. 21. Raj, G.V., et al., Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappa B. Prostate, 2004. 61(2): p. 105-113. 22. Hwang, Y.S., et al., Lysophosphatidic acid stimulates PC-3 prostate cancer cell matrigel invasion through activation of RhoA and NF-kappa B activity. Molecular Carcinogenesis, 2006. 45(7): p. 518-529. 23. Enholm, B., et al., Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene, 1997. 14(20): p. 2475-2483. 24. Lee, S.J., et al., LPA1 is essential for lymphatic vessel development in zebrafish. FASEB J, 2008. 22(10): p. 3706-15. 25. Lin, C.I., et al., Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappaB activation- and EGFR transactivation-dependent mechanisms. Cell Signal, 2008. 20(10): p. 1804-14. 26. Lin, C.I., et al., Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells. Cellular and Molecular Life Sciences, 2008. 65(17): p. 2740-2751. 27. Cohen, B., et al., Transcriptional Regulation of Vascular Endothelial Growth Factor C by Oxidative and Thermal Stress Is Mediated by Lens Epithelium-Derived Growth Factor/p75. Neoplasia, 2009. 11(9): p. 921-U271. 28. Rinaldo, F., et al., RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in prostate cancer cells during androgen ablation. Oncogene, 2007. 26(12): p. 1731-1738. 29. Sharma, P., et al., Activation of LEDGF gene by thermal-and oxidative-stresses. Biochem Biophys Res Commun, 2000. 276(3): p. 1320-4. 30. Shinohara, T., D.P. Singh, and N. Fatma, LEDGF, a survival factor, activates stress-related genes. Prog Retin Eye Res, 2002. 21(3): p. 341-58. 31. Mediavilla-Varela, M., et al., Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer, 2009. 8: p. 68. 32. Sapoznik, S., et al., Gonadotropin-regulated lymphangiogenesis in ovarian cancer is mediated by LEDGF-induced expression of VEGF-C. Cancer Res, 2009. 69(24): p. 9306-14. 33. Xie YH, Gibbs TC, Mukhin YV, Meier KE (2002) Role for 18 : 1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells. Journal of Biological Chemistry 277: 32516-32526. 34. Panupinthu N, Lee HY, Mills GB (2010) Lysophosphatidic acid production and action: critical new players in breast cancer initiation and progression. Br J Cancer 102: 941-946. 35. Kishi Y, Okudaira S, Tanaka M, Hama K, Shida D, et al. (2006) Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem 281: 17492-17500. 36. Ferry G, Moulharat N, Pradere JP, Desos P, Try A, et al. (2008) S32826, a nanomolar inhibitor of autotaxin: discovery, synthesis and applications as a pharmacological tool. J Pharmacol Exp Ther 327: 809-819. 37. Hao F, Tan M, Xu X, Han J, Miller DD, et al. (2007) Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha. Biochim Biophys Acta 1771: 883-892. 38. Park SY, Jeong KJ, Lee J, Yoon DS, Choi WS, et al. (2007) Hypoxia enhances LPA-induced HIF-1alpha and VEGF expression: their inhibition by resveratrol. Cancer Letters 258: 63-69. 39. Li J, Wang E, Rinaldo F, Datta K (2005) Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway. Oncogene 24: 5510-5520. 40. Aziziyeh AI, Li TT, Pape C, Pampillo M, Chidiac P, et al. (2009) Dual regulation of lysophosphatidic acid (LPA(1)) receptor signalling by Ral and GRK. Cellular Signalling 21: 1207-1217. 41. Lin CI, Chen CN, Huang MT, Lee SJ, Lin CH, et al. (2008) Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappa B activation- and EGFR transactivation-dependent mechanisms. Cellular Signalling 20: 1804-1814. 42. Daniels T, Zhang J, Gutierrez I, Elliot ML, Yamada B, et al. (2005) Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. Prostate 62: 14-26. 43. Zeng Y, Kakehi Y, Nouh M, Tsunemori H, Sugimoto M, et al. (2009) Gene expression Profiles of Lysophosphatidic Acid-Related Molecules in the Prostate: Relevance to Prostate Cancer and Benign Hyperplasia. Prostate 69: 283-292. 44. Rhim JH, Kim SA, Lee JE, Kim DJ, Chung HK, et al. (2008) Cancer cell-derived IL-1alpha induces IL-8 release in endothelial cells. J Cancer Res Clin Oncol 134: 45-50. 45. Reinmuth N, Rensinghoff S, Raedel M, Fehrmann N, Schwoppe C, et al. (2007) Paracrine interactions of vascular endothelial growth factor and platelet-derived growth factor in endothelial and lung cancer cells. Int J Oncol 31: 621-626. 46. Zeng Y, Opeskin K, Goad J, Williams ED (2006) Tumor-induced activation of lymphatic endothelial cells via vascular endothelial growth factor receptor-2 is critical for prostate cancer lymphatic metastasis. Cancer Res 66: 9566-9575. 47. Lin JM, Lalani AS, Harding TC, Gonzalez M, Wu WW, et al. (2005) Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor. Cancer Research 65: 6901-6909. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35628 | - |
dc.description.abstract | 在臨床研究中發現,前列腺癌惡化轉移和淋巴管新生 (Lymphangiogenesis)有一定的相關性。淋巴管生成因子 (VEGF-C)已知是造成淋巴管新生主要的蛋白質在本實驗的研究發現,在不同前列腺癌細胞株中,水解磷酸脂 (Lysophosphatidic acid) 會刺激淋巴管生成因子的轉錄和轉譯。在更進一步的研究中發現,水解淋酸脂的受器LPA1和LPA3會藉著調控過氧化物的生成 (Reactive Oxygen Species) 正向調控轉錄因子LEDGF的生成,最後刺激淋巴管生成因之的生成。不僅如此,結果也發現前列腺癌細胞中生成水解淋酸脂的酵素ATX也參與淋巴管生成因子
的調控。此發現有助於提供未來前列腺癌標把藥物治療的設計,將可能有效的阻止前列腺癌後期的淋巴轉移。 | zh_TW |
dc.description.abstract | ABSTRACT
Clinical evidence suggests that lymphangiogenesis and lymphatic metastasis are important processes during the progression of prostate cancer. Vascular endothelial growth factor (VEGF)-C was shown to be a key regulator in these processes. Our previous studies demonstrated that lysophosphatidic acid (LPA), a low-molecular-weight lipid growth factor, enhances VEGF-C expression in human endothelial cells. We previously demonstrated that the LPA receptor plays an important role in lymphatic development in zebrafish embryos. However, the effects of LPA on VEGF-C expression in prostate cancer are not known. Herein, we demonstrate that LPA up-regulated VEGF-C expression in three different human prostate cancer cell lines. In PC-3 human prostate cancer cells, the enhancing effects of LPA were mediated through both LPA1 and LPA3. In addition, reactive oxygen species (ROS) production and lens epithelium-derived growth factor (LEDGF) expression were involved in LPA1/3-dependent VEGF-C expression. Furthermore, autotaxin (ATX), an enzyme responsible for LPA synthesis, also participates in regulating VEGF-C expression. By interrupting LPA1/3 of PC-3, conditioned medium (CM) -induced human umbilical vein endothelial cell (HUVEC) lymphatic markers expression was also blocked. In summary, we found that LPA secreted by PC-3 cells enhanced VEGF-C expression through activating LPA1/3-, ROS-, and LEDGF-dependent pathways. These novel findings could potentially shed light on developing new strategies for preventing lymphatic metastasis of prostate cancer. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T07:01:55Z (GMT). No. of bitstreams: 1 ntu-100-R98b41023-1.pdf: 1739872 bytes, checksum: a6dc25a4c0ec104f25a368073e4cca46 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | CONTENTS
ABSTRACT…….……………………………………………1 INTRODUCTION…………………………………………...2 Prostate Cancer and Metastasis………………………………………2 Metastasis and Lymphangiogenesis in Prostate Cancer………………3 LPA and Lymphangiogenesis……………………….…………………4 RATIONALE…………………………………………………5 MATERIAL AND METHOD………………………………..6 Cell culture………………………………………………………6 LPA stimulation…………………………………………………..6 Western blot analysis………………………………………………7 Enzyme-linked immunosorbent assay (ELISA) ………………………7 Flow cytometry ………………………………………………….7 RNA isolation and reverse-transcription (RT) ………………………8 Quantitative real-time PCR………………………………………..8 shRNA and small-interfering (si)RNA transfection…………………..9 Statistical analysis………………………………………………..9 RESULTS…………………………………………………….10 LPA stimulates VEGF-C expression in different prostate cancer cell lines…………………………………………………………….10 LPA-enhanced VEGF-C expression is mediated through LPA1 and LPA3 in PC-3 cells……………………………………………………….10 LPA enhanced VEGF-C expression is ROS dependent……………....11 LPA1/3 mediates VEGF-C expression through inducing LEDGF……...12 Blockage of self-secreted LPA and knockdown of ATX expression reduce VEGF-C transcription and secretion by PC-3 cells…………………13 PC-3 conditioned medium induced HUVEC lymphatic marker expression through a LPA autocrine loop……………………………………..13 DISCUSSION………………………………………………...15 REFERENCE………………………………………………...18 FIGURES……………………………………………………..25 Figure 1…………………………………………………………25 Figure 2…………………………………………………………27 Figure 3…………………………………………………………29 Figure 4………………………………………………………....31 Figure 5………………………………………………………....33 Figure6…………………………………………………………35 Figure 7…………………………………………………………37 | |
dc.language.iso | en | |
dc.title | 在前列腺癌細胞中,水解磷酸脂自泌機轉調控淋巴管生成因子的訊號傳遞路徑 | zh_TW |
dc.title | Lysophosphatidic Acid Acts as an Autocrine Factor to Enhance Vascular Endothelial Growth Factor-C Expression in Human Prostate Cancer Cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳思原(Shee-Uan Chen),沈湯龍(Tang-Long Shen),丁詩同(Shih-Torng Ding) | |
dc.subject.keyword | 水解磷酸脂,淋巴管生成因子,前列腺癌, | zh_TW |
dc.subject.keyword | LPA,VEGF-C,Prostate Cancer, | en |
dc.relation.page | 37 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-20 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
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