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

Mauro Montalbano, Jeremias Georgiadis, Ashlyn L. Masterson, Joshua T. McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese

Research output: Contribution to journalReview article

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1291-1300
Number of pages10
JournalOncology Reports
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Glypicans
Hepatocytes
Hepatocellular Carcinoma
Liver
Proteins
Growth
Heparan Sulfate Proteoglycans
Cellular Structures
Immunotherapy
Cell Cycle
Down-Regulation
Biomarkers

Keywords

  • Cancer
  • Glypican-3
  • Hepatocarcinoma
  • Liver

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review). / Montalbano, Mauro; Georgiadis, Jeremias; Masterson, Ashlyn L.; McGuire, Joshua T.; Prajapati, Janika; Shirafkan, Ali; Rastellini, Cristiana; Cicalese, Luca.

In: Oncology Reports, Vol. 37, No. 3, 01.03.2017, p. 1291-1300.

Research output: Contribution to journalReview article

Montalbano, Mauro ; Georgiadis, Jeremias ; Masterson, Ashlyn L. ; McGuire, Joshua T. ; Prajapati, Janika ; Shirafkan, Ali ; Rastellini, Cristiana ; Cicalese, Luca. / Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review). In: Oncology Reports. 2017 ; Vol. 37, No. 3. pp. 1291-1300.
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AU - Georgiadis, Jeremias

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AU - McGuire, Joshua T.

AU - Prajapati, Janika

AU - Shirafkan, Ali

AU - Rastellini, Cristiana

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AB - 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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