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

@article{Montalbano2017BiologyAF,
  title={Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review).},
  author={Mauro Montalbano and Jeremias Georgiadis and Ashlyn L Masterson and Joshua T. McGuire and Janika Prajapati and Ali Mohammad Shirafkan and Cristiana Rastellini and Luca Cicalese},
  journal={Oncology reports},
  year={2017},
  volume={37 3},
  pages={
          1291-1300
        }
}
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… 
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Glypican-3 Enhances Reprogramming of Glucose Metabolism in Liver Cancer Cells
TLDR
It is demonstrated that GPC3 is a critical regulator of glucose metabolism reprogramming in LC cells, which provides a strong line of evidence for G PC3 as an important therapeutic target to normalize glucose metabolic aberrations responsible for LC progression.
The Expression of Glypican-3 in Colorectal Cancer
TLDR
Results indicated that GPC3 could be expressed in the CRC tissues at the mRNA level, while its expression could not be found at the protein level.
Diagnostic value of glypican-3, arginase-1 and hepatocyte paraffin antigen -1 in differentiating hepatocellular carcinoma from intrahepatic cholangiocarcinoma
TLDR
The combination models could improve the diagnosis value of HCC and help differentiating HCC from ICC and combined detection of GPC3, Arg-1 and HepPar-1 could increase the sensitivity up to 89.36% and the specificity to 100.00%, comparing with any single biomarker.
Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers
TLDR
This review will focus on detailing the multiple levels of epigenetic regulation of the enzymes in the heparan sulfate synthesis pathway with a particular focus on regulation by miRNA and effects of epigenetically regulated therapies on HSPGs.
An innovative peptide with high affinity to GPC3 for hepatocellular carcinoma diagnosis.
TLDR
The design of an innovative GPC3 targeting peptide (sequence: DYEMHLWWGTEL, denoted as IPA) is designed by using structure-based virtual simulation, showing promising prospects in detecting the expression of G PC3 for HCC targeting imaging.
Preparation and Characterization of Anti-GPC3 Nanobody Against Hepatocellular Carcinoma
TLDR
In vivo study showed that GPC3 nanobody suppresses the growth of HepG2 and improves the survival rate of tumor mice, suggesting a strong application potential for targeted therapy of liver cancer.
PiggyBac-engineered T cells expressing a glypican-3-specific chimeric antigen receptor show potent activities against hepatocellular carcinoma.
High GLYPICAN-3 expression Characterizes a Biologically Distinct subset of ovarian clear cell carcinomas in Canadian patients: An Opportunity for targeted Therapy.
Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice.
TLDR
In mice with xenograft or orthoptic liver tumors, CAR (hYP7) T cells eliminate GPC3-positive HCC cells, possibly by inducing perforin- and granzyme-mediated apoptosis or reducing Wnt signaling in tumor cells.
[10-gingerol inhibits proliferation of hepatocellular carcinoma HepG2 cells via Src/STAT3 signaling pathway].
TLDR
10-gingerol can dose-dependently inhibit the proliferation of HepG2 cells and suppress the activation of Src and STAT3.
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References

SHOWING 1-10 OF 59 REFERENCES
Glypican‐3: a marker and a therapeutic target in hepatocellular carcinoma
TLDR
Immunostaining of liver biopsies for GPC3 is currently being used by clinical pathologists to confirm HCC diagnosis when the malignant nature of the lesion is difficult to establish, and two therapeutic approaches for HCC are currently being tested in phase II clinical trials.
Investigation of the role of glypican 3 in liver regeneration and hepatocyte proliferation.
TLDR
The results indicate that GPC3 may be a negative regulator of liver regeneration and hepatocyte proliferation, and that this regulation may involve CD81.
Glypican-3 expression is silenced in human breast cancer
TLDR
The phenotype of the Simpson-Golabi-Behmel syndrome patients and GPC3-deficient mice, as well as gene transfection experiments indicate that G PC3 can act as an inhibitor of cell proliferation and survival, and data suggest that GPC2 can acts as a negative regulator of breast cancer growth.
Glypican‐3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP‐7 signaling
TLDR
Overexpression of GPC3 modulated cell proliferation by inhibiting fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 7 (BMP‐7) activity and an interaction of G PC3 and FGF2 was revealed by co‐immunoprecipitation, while GPC2 was found to inhibit B MP‐7 signaling through the Smad pathway by reporter gene assay.
Glypican-3: a new target for cancer immunotherapy.
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
TLDR
Evidence is presented indicating that OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma and breast cancer (II14 and MCF-7) and this induction, however, is cell line specific since it is not observed in NIH 3T3 fibroblasts or HT-29 colorectal tumor cells.
The role of glypican-3 in the regulation of body size and cancer
TLDR
The rationale that led to the hypothesize that GPC3 could be a negative regulator of Hedgehog signaling is discussed, and the implications of the discovery regarding the role of G PC3 in some cancer types are speculated.
Glypican 3: A Novel Marker in Testicular Germ Cell Tumors
TLDR
The findings suggest a possible role of GPC3 in tumor cell differentiation and GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.
Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker.
Novel Glypican-3-Binding Peptide for in Vivo Hepatocellular Carcinoma Fluorescent Imaging.
TLDR
A 12-mer peptide with the sequence of DHLASLWWGTEL (denoted as TJ12P1) was identified by screening a phage display peptide library that demonstrated ideal GPC3 binding affinity and used as a probe for HCC detection.
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