title: Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review).
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.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Montalbano
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Georgiadis
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Ashlyn L
authors.initials: AL
authors.lastname: Masterson
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: McGuire
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Janika
authors.initials: J
authors.lastname: Prajapati
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Shirafkan
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Rastellini
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Cicalese
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D053673:Glypicans / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans