Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
July-2018 Volume 16 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2018 Volume 16 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Elevated GPC3 level promotes cell proliferation in liver cancer

  • Authors:
    • Shanshan Wang
    • Ning Chen
    • Yuhan Chen
    • Lin Sun
    • Li Li
    • Hui Liu
  • View Affiliations / Copyright

    Affiliations: Beijing You'An Hospital Affiliated to Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, P.R. China, Department of Gastrointestinal and Hepatology, Beijing You'An Hospital Affiliated to Capital Medical University, Beijing 100069, P.R. China, Department of Pathology, Beijing You'An Hospital Affiliated to Capital Medical University, Beijing 100069, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 970-976
    |
    Published online on: May 21, 2018
       https://doi.org/10.3892/ol.2018.8754
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to investigate the biological role of glypican 3 (GPC3), and to identify its mechanism and clinical significance in the carcinogenesis of liver cancer. A total of 114 patients with liver cancer were involved. Their clinical data, hematoxylin and eosin‑stained and Antigen Ki‑67 protein (Ki‑67) and GPC3 immunohistochemically‑stained liver cancer tissue sections were analyzed to evaluate the correlation between the liver cancer proliferation, differentiation and GPC3 expression. Fluorescence microscopy, western blotting, MTT and reverse transcription quantitative polymerase chain reaction (RT‑qPCR) assays were performed in HepG2 and HLE cell lines to investigate the potential mechanisms of action. Among the 114 patients with liver cancer enrolled in the present study, 12 exhibited well‑differentiated liver cancer, of which 6 (50%) were positive for GPC3. A total of 30 cases exhibited poorly differentiated liver cancer; 26 (87%) of these expressed GPC3 and 11 cases (37%) demonstrated strong positive expression levels. The other 72 liver cancer cases were moderately differentiated; 75% (54/72) of these expressed GPC3 and 12.5% (9/72) exhibited strong positive expression levels. There was a significant association between the levels of GPC3 expression and liver cancer differentiation (χ2=16.306, P=0.008). Ki‑67 staining as the criteria of the liver cancer cell proliferation index also indicated a cross correlation between liver cancer proliferation and GPC3 levels. Among the 39 liver cancer samples with a cell proliferation index <5%, only 2.6% (1/39) exhibited strong positive GPC3 staining, but of the 16 cases with a high cell proliferation index >50%, 6 exhibited strong GPC3 staining (37.5%). The difference of cell proliferation indexes between cancer cells were well, moderate and poorly differentiated, and was markedly significant (χ2=26.334, P=0.002), and suggested that liver cancer cell proliferation was positively correlated with GPC3 expression (r=0.316, P=0.001). Consistently, in vitro analysis indicated that GPC3 promoted HepG2 and HLE cell growth, which was more apparent in HepG2 cells. The RT‑qPCR results indicated that GPC3 promoted proliferation through the Hedgehog (Hh) pathway in HepG2 cells, but not in HLE cells. In the present study, it was demonstrated that patients with liver cancer with higher GPC3 levels exhibited poorer differentiation and higher proliferation levels. In vitro GPC3 may promote liver cancer cell lines proliferation through the Hh pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Boily G, Ouellet S, Langlois S, Larivière M, Drouin R and Sinnett D: In vivo footprinting analysis of the Glypican 3 (GPC3) promoter region in neuroblastoma cells. Biochim Biophys Acta. 1769:182–193. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Filmus J and Selleck SB: Glypicans: Proteoglycans with a surprise. J Clin Invest. 108:497–501. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Filmus J, Capurro M and Rast J: Glypicans. GENOME BIOL 2008 2008-01-20. 9:224

4 

Capurro MI, Xu P, Shi W, Li F, Jia A and Filmus J: Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding. Dev Cell. 14:700–711. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Filmus J and Capurro M: The role of glypican-3 in the regulation of body size and cancer. Cell Cycle. 7:2787–2790. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Song HH and Filmus J: The role of glypicans in mammalian development. Biochim Biophys Acta. 1573:241–246. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A and Schlessinger D: Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 12:241–247. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Li M, Shuman C, Fei YL, Cutiongco E, Bender HA, Stevens C, Wilkins-Haug L, Day-Salvatore D, Yong SL, Geraghty MT, et al: GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome. Am J Med Genet. 102:161–168. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Nakatsura T, Kageshita T, Ito S, Wakamatsu K, Monji M, Ikuta Y, Senju S, Ono T and Nishimura Y: Identification of glypican-3 as a novel tumor marker for melanoma. Clin Cancer Res. 10:6612–6621. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Maeda D, Ota S, Takazawa Y, Aburatani H, Nakagawa S, Yano T, Taketani Y, Kodama T and Fukayama M: Glypican-3 expression in clear cell adenocarcinoma of the ovary. Mod Pathol. 22:824–832. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Zynger DL, Dimov ND, Luan C, Teh BT and Yang XJ: Glypican 3: A novel marker in testicular germ cell tumors. Am J Surg Pathol. 30:1570–1575. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Schmilovitz-Weiss H, Tobar A, Halpern M, Levy I, Shabtai E and Ben-Ari Z: Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: a historical prospective study. Diagn Pathol. 6:1212001. View Article : Google Scholar

13 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Gao JD, Shao YF, Xu Y, Ming LH, Wu ZY, Liu GT, Wang XH, Gao WH, Sun YT, Feng XL, et al: Tight association of hepatocellular carcinoma with HBV infection in North China. Hepatobiliary Pancreat Dis Int. 4:46–49. 2005.PubMed/NCBI

15 

Wang HL, Anatelli F, Zhai QJ, Adley B, Chuang ST and Yang XJ: Glypican-3 as a useful diagnostic marker that distinguishes hepatocellular carcinoma from benign hepatocellular mass lesions. Arch Pathol Lab Med. 132:1723–1728. 2008.PubMed/NCBI

16 

Bosman FT, Carneiro F, Hruban RH and Theise ND: WHO classification of tumours of the digestive system. 4th edition. Int Agen Res Cancer Lyon. 1089:2010.

17 

Shirakawa H, Kuronuma T, Nishimura Y, Hasebe T, Nakano M, Gotohda N, Takahashi S, Nakagohri T, Konishi M, Kobayashi N, et al: Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. Int J Oncol. 34:649–656. 2009.PubMed/NCBI

18 

López-Terrada D, Cheung SW, Finegold MJ and Knowles BB: Hep G2 is a hepatoblastoma-derived cell line. Hum Pathol. 40:1512–1525. 2009. View Article : Google Scholar

19 

Wang SS, Chen YH, Ning C, Wang LJ, Chen DX, Weng HL, Dooley S and Ding HG: Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway. Cell Death Dis. 8:e26882017. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Kawano Y, Sasaki A, Kai S, Endo Y, Iwaki K, Uchida H, Shibata K, Ohta M and Kitano S: Short- and long-term outcomes after hepatic resection for hepatocellular carcinoma with concomitant esophageal varices in patients with cirrhosis. Ann Surg Oncol. 15:1670–1676. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Liu H, Li P, Zhai Y, Qu CF, Zhang LJ, Tan YF, Li N and Ding HG: Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol. 16:4410–4415. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Iglesias BV, Centeno G, Pascuccelli H, Ward F, Peters MG, Filmus J, Puricelli L and de Kier Joffé EB: Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. Histol Histopathol. 23:1333–1340. 2008.PubMed/NCBI

24 

Jian R, Zheng DY and Luo RC: The expression of GPC3 in human malignant cancers and its potential clinical application. Tumor. 31:863–866. 2011.

25 

Suzuki M, Sugimoto K, Tanaka J, Tameda M, Inagaki Y, Kusagawa S, Nojiri K, Beppu T, Yoneda K, Yamamoto N, et al: Up-regulation of glypican-3 in human hepatocellular carcinoma. Anticancer Res. 30:5055–5061. 2010.PubMed/NCBI

26 

Lin Q, Xiong LW, Pan XF, Gen JF, Bao GL, Sha HF, Feng JX, Ji CY and Chen M: Expression of GPC3 protein and its significance in lung squamous cell carcinoma. Med Oncol. 29:663–669. 2012. View Article : Google Scholar : PubMed/NCBI

27 

An SJ, Huang YS, Chen ZH, Su J, Yang Y, Chen JG, Yan HH, Lin QX, Yang JJ, Yang XN, et al: Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy. Med Oncol. 29:627–632. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Mounajjed T, Zhang L and Wu TT: Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Hum Pathol. 44:542–550. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Valsechi MC, Oliveira AB, Conceição AL, Stuqui B, Candido NM, Provazzi PJ, de Araújo LF, Silva WA Jr, Calmon Mde F and Rahal P: GPC3 reduces cell proliferation in renal carcinoma cell lines. BMC Cancer. 14:6312014. View Article : Google Scholar : PubMed/NCBI

30 

Stigliano I, Puricelli L, Filmus J, Sogayar MC, Bal de Kier Joffé E and Peters MG: Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation. Breast Cancer Res Treat. 114:251–262. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Gao W and Ho M: The role of glypican-3 in regulating Wnt in hepatocellular carcinomas. Cancer Rep. 1:14–19. 2011.PubMed/NCBI

32 

Pan Z, Chen C, Long H, Lei C, Tang G, Li L, Feng J and Chen F: Overexpression of GPC3 inhibits hepatocellular carcinoma cell proliferation and invasion through induction of apoptosis. Mol Med Rep. 7:969–974. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Sakurai M, Shibata K, Umezu T, Kajiyama H, Yamamoto E, Ino K, Nawa A and Kikkawa F: Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells. Gynecol Oncol. 119:332–336. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Miao HL, Pan ZJ, Lei CJ, Wen JY, Li MY, Liu ZK, Qiu ZD, Lin MZ, Chen NP and Chen M: Knockdown of GPC3 inhibits the proliferation of Huh7 hepatocellular carcinoma cells through down-regulation of YAP. J Cell Biochem. 114:625–631. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang S, Chen N, Chen Y, Sun L, Li L and Liu H: Elevated GPC3 level promotes cell proliferation in liver cancer. Oncol Lett 16: 970-976, 2018.
APA
Wang, S., Chen, N., Chen, Y., Sun, L., Li, L., & Liu, H. (2018). Elevated GPC3 level promotes cell proliferation in liver cancer. Oncology Letters, 16, 970-976. https://doi.org/10.3892/ol.2018.8754
MLA
Wang, S., Chen, N., Chen, Y., Sun, L., Li, L., Liu, H."Elevated GPC3 level promotes cell proliferation in liver cancer". Oncology Letters 16.1 (2018): 970-976.
Chicago
Wang, S., Chen, N., Chen, Y., Sun, L., Li, L., Liu, H."Elevated GPC3 level promotes cell proliferation in liver cancer". Oncology Letters 16, no. 1 (2018): 970-976. https://doi.org/10.3892/ol.2018.8754
Copy and paste a formatted citation
x
Spandidos Publications style
Wang S, Chen N, Chen Y, Sun L, Li L and Liu H: Elevated GPC3 level promotes cell proliferation in liver cancer. Oncol Lett 16: 970-976, 2018.
APA
Wang, S., Chen, N., Chen, Y., Sun, L., Li, L., & Liu, H. (2018). Elevated GPC3 level promotes cell proliferation in liver cancer. Oncology Letters, 16, 970-976. https://doi.org/10.3892/ol.2018.8754
MLA
Wang, S., Chen, N., Chen, Y., Sun, L., Li, L., Liu, H."Elevated GPC3 level promotes cell proliferation in liver cancer". Oncology Letters 16.1 (2018): 970-976.
Chicago
Wang, S., Chen, N., Chen, Y., Sun, L., Li, L., Liu, H."Elevated GPC3 level promotes cell proliferation in liver cancer". Oncology Letters 16, no. 1 (2018): 970-976. https://doi.org/10.3892/ol.2018.8754
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team