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. 2005 Aug 19;94(3):259–262. doi: 10.1111/j.1349-7006.2003.tb01430.x

Glypican‐3 is overexpressed in human hepatocellular carcinoma

Young Kwan Sung 1, Sun Young Hwang 1, Mi Kyung Park 1, Mohammad Farooq 1, In Sook Han 1, Han Ik Bae 2, Jung‐Chul Kim 1, Moonkyu Kim 1,3
PMCID: PMC11160150  PMID: 12824919

Abstract

To identify candidate genes that could be used as diagnostic and therapeutic targets for hepatocellular carcinoma (HCC), we searched for the genes that are overexpressed in HCC by combining representational difference analysis and microarray. Genes such as glypican‐3 (GPC3), insulin‐like growth factor 2, long‐chain fatty‐acid‐coenzyme A ligase 4, farnesyl diphosphate synthase were frequently identified in our screening. Northern blot analysis with these four genes confirmed their overexpression in HCC. Among them we found that GPC3 transcript is upregulated in six out of seven cases of HCC. Immunoblot and immunohistochemical staining using polyclonal anti‐GPC3 antibodies further confirmed that GPC3 protein is indeed increased in HCC tumor samples. We also found that GPC3 is secreted into culture media from cell lines derived from HCC. We conclude that GPC3 is a good molecular marker for HCC. (Cancer Sci 2003; 94: 259–262)

References

  • 1. Filmus J, Shi W, Wong ZM, Wong MJ. Identification of a new membrane‐bound heparan sulphate proteoglycan. Biochem. J 1995; 311: 561–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Pilia G, Hughes‐Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D. Mutations in GPC3, a glypican gene, cause the Simpson‐Golabi‐Behmel overgrowth syndrome. Nat Genet 1996; 12: 241–7. [DOI] [PubMed] [Google Scholar]
  • 3. Cano‐Gauci DF, Song HH, Yang H, McKerlie C, Choo B, Shi W, Pullano R, Piscione TD, Grisaru S, Soon S, Sedlackova L, Tanswell AK, Mak TW, Yeger H, Lockwood GA, Rosenblum ND, Filmus J. Glypican‐3‐deficient mice exhibit developmental overgrowth and some of the abnormalities typical of Simpson‐Golabi‐Behmel syndrome. J Cell Biol 1999; 146: 255–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Paine‐Saunders S, Viviano BL, Zupicich J, Skarnes WC, Saunders S. Glypican‐3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Dev Biol 2000; 225: 179–87. [DOI] [PubMed] [Google Scholar]
  • 5. Chiao E, Fisher P, Crisponi L, Deiana M, Dragatsis I, Schlessinger D, Pilia G, Efstratiadis A. Overgrowth of a mouse model of the Simpson‐Golabi‐Behmel syndrome is independent of IGF signaling. Dev Biol 2002; 243: 185–206. [DOI] [PubMed] [Google Scholar]
  • 6. Gonzalez AD, Kaya M, Shi W, Song H, Testa JR, Penn LZ, Filmus J. OCI‐5/ GPC3, a glypican encoded by a gene that is mutated in the Simpson‐Golabi‐Behmel overgrowth syndrome, induces apoptosis in a cell line‐specific manner. J Cell Biol 1998; 141: 1407–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Lin H, Huber R, Schlessinger D, Morin PJ. Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res 1999; 59: 807–10. [PubMed] [Google Scholar]
  • 8. Murthy SS, Shen T, De Rienzo A, Lee WC, Ferriola PC, Jhanwar SC, Mossman BT, Filmus J, Testa JR. Expression of GPC3, an X‐linked recessive overgrowth gene, is silenced in malignant mesothelioma. Oncogene 2000; 19: 410–6. [DOI] [PubMed] [Google Scholar]
  • 9. Xiang YY, Ladeda V, Filmus J. Glypican‐3 expression is silenced in human breast cancer. Oncogene 2001; 20: 7408–12. [DOI] [PubMed] [Google Scholar]
  • 10. Hsu HC, Cheng W, Lai PL. Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution. Cancer Res 1997; 57: 5179–84. [PubMed] [Google Scholar]
  • 11. Zhu ZW, Friess H, Wang L, Abou‐Shady M, Zimmermann A, Lander AD, Korc M, Kleeff J, Buchler MW. Enhanced glypican‐3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut 2001; 48: 558–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Saikali Z, Sinnett D. Expression of glypican 3 (GPC3) in embryonal tumors. Int J Cancer 2000; 89: 418–22. [PubMed] [Google Scholar]
  • 13. Lisitsyn N, Wigler M. Cloning the differences between two complex genomes. Science 1993; 259: 946–51. [DOI] [PubMed] [Google Scholar]
  • 14. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 1996; 14: 457–60. [DOI] [PubMed] [Google Scholar]
  • 15. Park JG, Lee JH, Kang MS, Park KJ, Jeon YM, Lee HJ, Kwon HS, Park HS, Yeo KS, Lee KU, Kim ST, Chung JK, Hwang YJ, Lee HS, Kim CY, Lee YI, Chen TR, Hay RJ, Song SY, Kim WH, Kim CW, Kim YI. Characterization of cell lines established from human hepatocellular carcinoma. Int J Cancer 1995; 62: 276–82. [DOI] [PubMed] [Google Scholar]
  • 16. Hubank M, Schatz DG. Identifying differences in mRNA expression by representational difference analysis of cDNA. Nucleic Acids Res 1994; 22: 5640–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Chung EJ, Sung YK, Farooq M, Kim YH, Tak WY, Hwang YJ, Kim YI, Han HS, Kim JC, Kim MK. Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray. Mol Cells 2002; 14: 382–7. [PubMed] [Google Scholar]
  • 18. Sung YK, Moon C, Yoo JY, Moon C, Pearse D, Pevsner J, Ronnett GV. Plunc, a member of the secretory gland protein family, is up‐regulated in nasal respiratory epithelium after olfactory bulbectomy. J Biol Chem 2002; 277: 12762–9. [DOI] [PubMed] [Google Scholar]
  • 19. Liu W, Litwack ED, Stanley MJ, Langford JK, Lander AD, Sanderson RD. Heparan sulfate proteoglycans as adhesive and anti‐invasive molecules. Syn‐decans and glypican have distinct functions. J Biol Chem 1998; 273: 22825–32. [DOI] [PubMed] [Google Scholar]
  • 20. Cao Y, Dave KB, Doan TP, Prescott SM. Fatty acid CoA ligase 4 is up‐regulated in colon adenocarcinoma. Cancer Res 2001; 61: 8429–34. [PubMed] [Google Scholar]
  • 21. Foo NC, Yen TS. Activation of promoters for cellular lipogenic genes by hepatitis B virus large surface protein. Virology 2000; 269: 420–5. [DOI] [PubMed] [Google Scholar]
  • 22. Cariani E, Lasserre C, Seurin D, Hamelin B, Kemeny F, Franco D, Czech MP, Ullrich A, Brechot C. Differential expression of insulin‐like growth factor II mRNA in human primary liver cancers, benign liver tumors, and liver cirrhosis. Cancer Res 1988; 48: 6844–9. [PubMed] [Google Scholar]
  • 23. Mast AE, Higuchi DA, Huang ZF, Warshawsky I, Schwartz AL, Broze GJ Jr. Glypican‐3 is a binding protein on the HepG2 cell surface for tissue factor pathway inhibitor. Biochem. J 1997; 327: 577–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Filmus J, Selleck SB. Glypicans: proteoglycans with a surprise. J Clin Invest 2001; 108: 497–501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Coggin JH Jr. The implications of embryonic gene expression in neoplasia. Crit Rev Oncol Hematol 1986; 5: 37–55. [DOI] [PubMed] [Google Scholar]
  • 26. Matsuura H, Hakomori S. The oncofetal domain of fibronectin defined by monoclonal antibody FDC‐6: its presence in fibronectins from fetal and tumor tissues and its absence in those from normal adult tissues and plasma. Proc Natl Acad Sci USA 1985; 82: 6517–21. [DOI] [PMC free article] [PubMed] [Google Scholar]

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