GPC3 reduces cell proliferation in renal carcinoma cell lines

详细信息    查看全文

• 作者：Marina Curado Valsechi (29)
  Ana Beatriz Bortolozo Oliveira (29)
  Andr茅 Luis Giacometti Concei莽茫o (29)
  Bruna Stuqui (29)
  Natalia Maria Candido (29)
  Paola Jocelan Scarin Provazzi (29)
  Luiza Ferreira de Ara煤jo (30)
  Wilson Ara煤jo Silva Jr (30)
  Marilia de Freitas Calmon (29)
  Paula Rahal (29)
  
  29. Department of Biology ; Instituto de Bioci锚ncias ; Letras e Ci锚ncias Exatas - IBILCE/UNESP ; Rua Crist贸v茫o Colombo ; 2265 ; 15054-000 ; S茫o Jos茅 do Rio Preto ; SP ; Brazil
  30. Department of Genetics ; University of S茫o Paulo ; and Center for Integrative Systems Biology (CISBi-NAP/USP) ; Av. Bandeirantes ; 14049-900 ; Ribeir茫o Preto - S茫o Paulo ; Brazil
  
• 关键词：GPC3 ; Cell lines ; Cell proliferation ; Renal carcinoma ; Transfection
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,502 KB
• 参考文献：1. Xue, YJ, Xiao, RH, Long, DZ, Zou, XF, Wang, XN, Zhang, GX, Yuan, YH, Wu, GQ, Yang, J, Wu, YT, Xu, H, Liu, FL, Liu, M (2012) Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma. J Transl Med 10: pp. 200 CrossRef
  2. Xu, L, Zhu, Y, Xu, J, Wu, K, Li, J, Xu, W, Liu, H, Wang, S, Yin, H, Chen, L, Wang, G, Lin, Z (2012) Notch1 activation promotes renal cell carcinoma growth via PI3K/Akt signaling. Cancer Sci 103: pp. 1253-1258 CrossRef
  3. Van Poppel, H, Becker, F, Cadeddu, JA, Gill, IS, Janetschek, G, Jewett, MA, Laguna, MP, Marberger, M, Montorsi, F, Polascik, TJ, Ukimura, O, Zhu, G (2011) Treatment of localised renal cell carcinoma. Eur Urol 60: pp. 662-672 CrossRef
  4. Drucker, BJ (2005) Renal cell carcinoma: current status and future prospects. Cancer Treat Rev 31: pp. 536-545 CrossRef
  5. Martignoni, G, Brunelli, M, Gobbo, S, Remo, A, Ficarra, V, Cossu-Rocca, P, Pea, M, Chilosi, M, Menestrina, F, Cheng, L (2007) Role of molecular markers in diagnosis and prognosis of renal cell carcinoma. Anal Quant Cytol Histol 29: pp. 41-49
  6. Lang, K, Danchenko, N, Gondek, K, Schwartz, B, Thompson, D (2007) The burden of illness associated with renal cell carcinoma in the United States. Urol Oncol 25: pp. 368-375 CrossRef
  7. Girgis, AH, Iakovlev, VV, Beheshti, B, Bayani, J, Squire, JA, Bui, A, Mankaruos, M, Youssef, Y, Khalil, B, Khella, H, Pasic, M, Yousef, GM (2012) Multilevel whole-genome analysis reveals candidate biomarkers in clear cell renal cell carcinoma. Cancer Res 72: pp. 5273-5284 0008-5472.CAN-12-0656" target="_blank" title="It opens in new window">CrossRef
  8. Wood, LS (2007) Managing the Complex Journey of Renal Cell Carcinoma. Spotlight on Symposia from the ONS 32nd Annual Congress: 2007; Las Vegas, NV.
  9. Takahashi, M, Rhodes, DR, Furge, KA, Kanayama, H, Kagawa, S, Haab, BB, Teh, BT (2001) Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification. Proc Natl Acad Sci U S A 98: pp. 9754-9759 CrossRef
  10. Moch, H (2013) An overview of renal cell cancer: pathology and genetics. Semin Cancer Biol 23: pp. 3-9 CrossRef
  11. Nickerson, ML, Jaeger, E, Shi, Y, Durocher, JA, Mahurkar, S, Zaridze, D, Matveev, V, Janout, V, Kollarova, H, Bencko, V, Navratilova, M, Szeszenia-Dabrowska, N, Mates, D, Mukeria, A, Holcatova, I, Schmidt, LS, Toro, JR, Karami, S, Hung, R, Gerard, GF, Linehan, WM, Merino, M, Zbar, B, Boffetta, P, Brennan, P, Rothman, N, Chow, WH, Waldman, FM, Moore, LE (2008) Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clin Cancer Res 14: pp. 4726-4734 CrossRef
  12. Hirota, E, Yan, L, Tsunoda, T, Ashida, S, Fujime, M, Shuin, T, Miki, T, Nakamura, Y, Katagiri, T (2006) Genome-wide gene expression profiles of clear cell renal cell carcinoma: identification of molecular targets for treatment of renal cell carcinoma. Int J Oncol 29: pp. 799-827
  13. Yu, G, Yao, W, Wang, J, Ma, X, Xiao, W, Li, H, Xia, D, Yang, Y, Deng, K, Xiao, H, Wang, B, Guo, X, Guan, W, Hu, Z, Bai, Y, Xu, H, Liu, J, Zhang, X, Ye, Z (2012) LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray. PLoS ONE 7: pp. e42377 CrossRef
  14. Liu, B, Bell, AW, Paranjpe, S, Bowen, WC, Khillan, JS, Luo, JH, Mars, WM, Michalopoulos, GK (2010) Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice. Hepatology 52: pp. 1060-1067 CrossRef
  15. Sawada, Y, Sakai, M, Yoshikawa, T, Ofuji, K, Nakatsura, T (2012) A glypican-3-derived peptide vaccine against hepatocellular carcinoma. Oncoimmunology 1: pp. 1448-1450 CrossRef
  16. Kohashi, K, Nakatsura, T, Kinoshita, Y, Yamamoto, H, Yamada, Y, Tajiri, T, Taguchi, T, Iwamoto, Y, Oda, Y (2013) Glypican 3 expression in tumors with loss of SMARCB1/INI1 protein expression. Hum Pathol 44: pp. 526-533 CrossRef
  17. Wang, YL, Zhu, ZJ, Teng, DH, Yao, Z, Gao, W, Shen, ZY (2012) Glypican-3 expression and its relationship with recurrence of HCC after liver transplantation. World J Gastroenterol 18: pp. 2408-2414 CrossRef
  18. Ho, M, Kim, H (2011) Glypican-3: a new target for cancer immunotherapy. Eur J Cancer 47: pp. 333-338 CrossRef
  19. Lin, H, Huber, R, Schlessinger, D, Morin, PJ (1999) Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res 59: pp. 807-810
  20. Xiang, YY, Ladeda, V, Filmus, J (2001) Glypican-3 expression is silenced in human breast cancer. Oncogene 20: pp. 7408-7412 CrossRef
  21. Li, L, Jin, R, Zhang, X, Lv, F, Liu, L, Liu, D, Liu, K, Li, N, Chen, D (2012) Oncogenic activation of glypican-3 by c-Myc in human hepatocellular carcinoma. Hepatology 56: pp. 1380-1390 CrossRef
  22. Sun, CK, Chua, MS, He, J, So, SK (2011) Suppression of glypican 3 inhibits growth of hepatocellular carcinoma cells through up-regulation of TGF-beta2. Neoplasia 13: pp. 735-747
  TNM Classification of Malignant Tumors.
  23. Pfaffl, MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: pp. e45 CrossRef
  24. Umezu, T, Shibata, K, Shimaoka, M, Kajiyama, H, Yamamoto, E, Ino, K, Nawa, A, Senga, T, Kikkawa, F (2010) Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo. Cancer Sci 101: pp. 143-148 CrossRef
  25. Liu, S, Li, Y, Chen, W, Zheng, P, Liu, T, He, W, Zhang, J, Zeng, X (2012) Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 419: pp. 656-661 CrossRef
  26. Liu, D, Shriver, Z, Qi, Y, Venkataraman, G, Sasisekharan, R (2002) Dynamic regulation of tumor growth and metastasis by heparan sulfate glycosaminoglycans. Semin Thromb Hemost 28: pp. 67-78 CrossRef
  27. Sanderson, RD (2001) Heparan sulfate proteoglycans in invasion and metastasis. Semin Cell Dev Biol 12: pp. 89-98 000.0241" target="_blank" title="It opens in new window">CrossRef
  28. Lin, CW, Mars, WM, Paranjpe, S, Donthamsetty, S, Bhave, VS, Kang, LI, Orr, A, Bowen, WC, Bell, AW, Michalopoulos, GK (2011) Hepatocyte proliferation and hepatomegaly induced by phenobarbital and 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene is suppressed in hepatocyte-targeted glypican 3 transgenic mice. Hepatology 54: pp. 620-630 CrossRef
  29. Esheba, GE, Pate, LL, Longacre, TA (2008) Oncofetal protein glypican-3 distinguishes yolk sac tumor from clear cell carcinoma of the ovary. Am J Surg Pathol 32: pp. 600-607 CrossRef
  30. Buchanan, C, Stigliano, I, Garay-Malpartida, HM, Rodrigues Gomes, L, Puricelli, L, Sogayar, MC, Bal De Kier Joffe, E, Peters, MG (2010) Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3K/Akt and p38MAPK signaling pathways. Breast Cancer Res Treat 119: pp. 559-574 CrossRef
  31. Tsuta, K, Tanabe, Y, Yoshida, A, Takahashi, F, Maeshima, AM, Asamura, H, Tsuda, H (2011) Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the Lung. J Thorac Oncol 6: pp. 1190-1199 CrossRef
  32. Capurro, M, Wanless, IR, Sherman, M, Deboer, G, Shi, W, Miyoshi, E, Filmus, J (2003) Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 125: pp. 89-97 CrossRef
  33. Liu, H, Li, P, Zhai, Y, Qu, CF, Zhang, LJ, Tan, YF, Li, N, Ding, HG (2010) Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol 16: pp. 4410-4415 CrossRef
  34. Zhang, L, Liu, H, Sun, L, Li, N, Ding, H, Zheng, J (2012) Glypican-3 as a potential differential diagnosis marker for hepatocellular carcinoma: a tissue microarray-based study. Acta Histochem 114: pp. 547-552 CrossRef
  35. Aviel-Ronen, S, Lau, SK, Pintilie, M, Lau, D, Liu, N, Tsao, MS, Jothy, S (2008) Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma. Mod Pathol 21: pp. 817-825 CrossRef
  36. Chan, ES, Pawel, BR, Corao, DA, Venneti, S, Russo, P, Santi, M, Sullivan, LM (2013) Immunohistochemical expression of glypican-3 in pediatric tumors: an analysis of 414 cases. Pediatr Dev Pathol 16: pp. 272-277 CrossRef
  37. Gailey, MP, Bellizzi, AM (2013) Immunohistochemistry for the novel markers glypican 3, PAX8, and p40 (DeltaNp63) in squamous cell and urothelial carcinoma. Am J Clin Pathol 140: pp. 872-880 CrossRef
  38. Okon, K (2008) Glypican-3 is expressed in chromophobe renal cell carcinomas. Pol J Pathol 59: pp. 15-20
  39. Murthy, SS, Shen, T, De Rienzo, A, Lee, WC, Ferriola, PC, Jhanwar, SC, Mossman, BT, Filmus, J, Testa, JR (2000) Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma. Oncogene 19: pp. 410-416 CrossRef
  40. Gao, W, Ho, M (2011) The role of glypican-3 in regulating Wnt in hepatocellular carcinomas. Cancer Rep 1: pp. 14-19
  41. Midorikawa, Y, Ishikawa, S, Iwanari, H, Imamura, T, Sakamoto, H, Miyazono, K, Kodama, T, Makuuchi, M, Aburatani, H (2003) Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling. Int J Cancer 103: pp. 455-465 CrossRef
  42. Miao, HL, Pan, ZJ, Lei, CJ, Wen, JY, Li, MY, Liu, ZK, Qiu, ZD, Lin, MZ, Chen, NP, Chen, M (2013) Knockdown of GPC3 inhibits the proliferation of Huh7 hepatocellular carcinoma cells through down-regulation of YAP. J Cell Biochem 114: pp. 625-631 CrossRef
  43. Hanahan, D, Weinberg, RA (2000) The hallmarks of cancer. Cell 100: pp. 57-70 CrossRef
  44. Farooq, M, Hwang, SY, Park, MK, Kim, JC, Kim, MK, Sung, YK (2003) Blocking endogenous glypican-3 expression releases Hep 3B cells from G1 arrest. Mol Cells 15: pp. 356-360
  45. Robinson, J, Viti, M, Hook, M (1984) Structure and properties of an under-sulfated heparan sulfate proteoglycan synthesized by a rat hepatoma cell line. J Cell Biol 98: pp. 946-953 CrossRef
  46. Kure, S, Yoshie, O, Aso, H (1987) Metastatic potential of murine B16 melanoma correlates with reduced surface heparan sulfate glycosaminoglycan. Jpn J Cancer Res 78: pp. 1238-1245
  47. Moczar, M, Caux, F, Bailly, M, Berthier, O, Dore, JF (1993) Accumulation of heparan sulfate in the culture of human melanoma cells with different metastatic ability. Clin Exp Metastasis 11: pp. 462-471 00054937" target="_blank" title="It opens in new window">CrossRef
  48. Zhu, ZW, Friess, H, Wang, L, Abou-Shady, M, Zimmermann, A, Lander, AD, Korc, M, Kleeff, J, Buchler, MW (2001) Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut 48: pp. 558-564 CrossRef
  49. Peters, MG, Farias, E, Colombo, L, Filmus, J, Puricelli, L, Bal De Kier Joffe, E (2003) Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model. Breast Cancer Res Treat 80: pp. 221-232 CrossRef
  50. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/631/prepub
  
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

Background Glypican 3 (GPC3) is a member of the family of glypican heparan sulfate proteoglycans (HSPGs). The GPC3 gene may play a role in controlling cell migration, negatively regulating cell growth and inducing apoptosis. GPC3 is downregulated in several cancers, which can result in uncontrolled cell growth and can also contribute to the malignant phenotype of some tumors. The purpose of this study was to analyze the mechanism of action of the GPC3 gene in clear cell renal cell carcinoma. Methods Five clear cell renal cell carcinoma cell lines and carcinoma samples were used to analyze GPC3 mRNA expression (qRT-PCR). Then, representative cell lines, one primary renal carcinoma (786-O) and one metastatic renal carcinoma (ACHN), were chosen to carry out functional studies. We constructed a GPC3 expression vector and transfected the renal carcinoma cell lines, 786-O and ACHN. GPC3 overexpression was analyzed using qRT-PCR and immunocytochemistry. We evaluated cell proliferation using MTT and colony formation assays. Flow cytometry was used to evaluate apoptosis and perform cell cycle analyses. Results We observed that GPC3 is downregulated in clear cell renal cell carcinoma samples and cell lines compared with normal renal samples. GPC3 mRNA expression and protein levels in 786-O and ACHN cell lines increased after transfection with the GPC3 expression construct, and the cell proliferation rate decreased in both cell lines following overexpression of GPC3. Further, apoptosis was not induced in the renal cell carcinoma cell lines overexpressing GPC3, and there was an increase in the cell population during the G1 phase in the cell cycle. Conclusion We suggest that the GPC3 gene reduces the rate of cell proliferation through cell cycle arrest during the G1 phase in renal cell carcinoma.