Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review)

  • Authors:
    • Mauro Montalbano
    • Jeremias Georgiadis
    • Ashlyn L. Masterson
    • Joshua T. McGuire
    • Janika Prajapati
    • Ali Shirafkan
    • Cristiana Rastellini
    • Luca Cicalese
  • View Affiliations

  • Published online on: January 18, 2017     https://doi.org/10.3892/or.2017.5387
  • Pages:1291-1300
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Abstract

Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome. Additionally, certain cancer types have displayed a downregulation of GPC-3 expression. More recently, the protein has been evaluated as a useful marker for hepatocellular carcinoma (HCC) due to its increased expression in the liver during times of growth. In contrast, the GPC-3 marker is not detectable in normal adult liver. Immunotherapy that targets GPC-3 and its affiliated proteins is under investigation as these new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed. Studies have reported that an overexpression of GPC-3 in HCC predicts a poorer prognosis. This prognostic value further pushes the question regarding GPC-3's role in the regulation and progression of HCC. This review will summarize the current knowledge regarding the clinical aspects of GPC-3, while also synthesizing the current literature with the aim to better understand this molecule's biological interactions at a molecular level, not only in the liver, but in the rest of the body as well. Due to the existing gap in the literature surrounding GPC-3, we believe further investigation of function, structure and domains, cellular localization, and other subfields is warranted to evaluate the protein as a whole, as well as its part in the study of HCC.

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March 2017
Volume 37 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Montalbano, M., Georgiadis, J., Masterson, A.L., McGuire, J.T., Prajapati, J., Shirafkan, A. ... Cicalese, L. (2017). Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review). Oncology Reports, 37, 1291-1300. https://doi.org/10.3892/or.2017.5387
MLA
Montalbano, M., Georgiadis, J., Masterson, A. L., McGuire, J. T., Prajapati, J., Shirafkan, A., Rastellini, C., Cicalese, L."Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review)". Oncology Reports 37.3 (2017): 1291-1300.
Chicago
Montalbano, M., Georgiadis, J., Masterson, A. L., McGuire, J. T., Prajapati, J., Shirafkan, A., Rastellini, C., Cicalese, L."Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review)". Oncology Reports 37, no. 3 (2017): 1291-1300. https://doi.org/10.3892/or.2017.5387