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Clinical and Translational Medicine
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Open Access 01-12-2017 | Review

Can glypican-3 be a disease-specific biomarker?

Authors: Chaolei Chen, Xiaomin Huang, Zhaojian Ying, Dengmin Wu, Yani Yu, Xiangdong Wang, Chengshui Chen

Published in: Clinical and Translational Medicine | Issue 1/2017

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Abstract

Background

Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been identified as a potential biomarker candidate in hepatocellular carcinoma, lung carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The aim of our review is to evaluate whether GPC3 has utility as a disease-specific biomarker, to discuss the potential involvement of GPC3 in cell biology, and to consider the changes of GPC3 gene and protein expression and regulation in hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS.

Results

Immunohistochemical studies have suggested that over-expression of GPC3 is associated with a poorer prognosis for hepatocellular carcinoma patients. Expression of GPC3 leads to an increased apoptosis response in human lung carcinoma tumor cells, and is considered to be a candidate lung tumor suppressor gene. Increased serum levels of GPC3 have been demonstrated in ARDS patients with severe pneumonia.

Conclusions

Glypican-3 could be considered as a clinically useful biomarker in hepatocellular carcinoma, lung carcinoma, and ARDS, but further research is needed to confirm and expand on these findings.
Literature
1.
Definition Task Force ARDS, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307(23):2526–2533
2.
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A, Investigators LS, Group ET (2016) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 315(8):788–800CrossRefPubMed
3.
Chen C, Shi L, Li Y, Wang X, Yang S (2016) Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia. Cell Biol Toxicol 32(3):169–184CrossRefPubMedPubMedCentral
4.
Nakatsura T, Yoshitake Y, Senju S, Monji M, Komori H, Motomura Y, Hosaka S, Beppu T, Ishiko T, Kamohara H, Ashihara H, Katagiri T, Furukawa Y, Fujiyama S, Ogawa M, Nakamura Y, Nishimura Y (2003) Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun 306(1):16–25CrossRefPubMed
5.
6.
Truedsson M, Malm J, Barbara Sahlin K, Bugge M, Wieslander E, Dahlback M, Appelqvist R, Fehniger TE, Marko-Varga G (2016) Biomarkers of early chronic obstructive pulmonary disease (COPD) in smokers and former smokers. Protocol of a longitudinal study. Clin Transl Med 5(1):9CrossRefPubMedPubMedCentral
7.
Wu D, Wang X (2015) Application of clinical bioinformatics in lung cancer-specific biomarkers. Cancer Metastasis Rev 34(2):209–216CrossRefPubMed
8.
9.
Filmus J, Church JG, Buick RN (1988) Isolation of a cDNA corresponding to a developmentally regulated transcript in rat intestine. Mol Cell Biol 8(10):4243–4249CrossRefPubMedPubMedCentral
10.
Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D (1996) Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet 12(3):241–247CrossRefPubMed
11.
Bulow HE, Hobert O (2006) The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol 22:375–407CrossRefPubMed
12.
13.
Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, Tokita S, Iwanari H, Ito Y, Nakano K, Nezu J, Tsunoda H, Yoshino T, Ohizumi I, Tsuchiya M, Ohnishi S, Makuuchi M, Hamakubo T, Kodama T, Aburatani H (2004) Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res 64(7):2418–2423CrossRefPubMed
14.
De Cat B, Muyldermans SY, Coomans C, Degeest G, Vanderschueren B, Creemers J, Biemar F, Peers B, David G (2003) Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements. J Cell Biol 163(3):625–635CrossRefPubMedPubMedCentral
15.
Traister A, Shi W, Filmus J (2008) Mammalian Notum induces the release of glypicans and other GPI-anchored proteins from the cell surface. Biochem J 410(3):503–511CrossRefPubMed
16.
Iglesias BV, Centeno G, Pascuccelli H, Ward F, Peters MG, Filmus J, Puricelli L, de Kier Joffe EB (2008) Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. Histol Histopathol 23(11):1333–1340PubMed
17.
Pellegrini M, Pilia G, Pantano S, Lucchini F, Uda M, Fumi M, Cao A, Schlessinger D, Forabosco A (1998) Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome. Dev Dyn 213(4):431–439CrossRefPubMed
18.
Song HH, Shi W, Xiang YY, Filmus J (2005) The loss of glypican-3 induces alterations in Wnt signaling. J Biol Chem 280(3):2116–2125CrossRefPubMed
19.
Grisaru S, Cano-Gauci D, Tee J, Filmus J, Rosenblum ND (2001) Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis. Dev Biol 231(1):31–46CrossRefPubMed
20.
Dwivedi PP, Lam N, Powell BC (2013) Boning up on glypicans—opportunities for new insights into bone biology. Cell Biochem Funct 31(2):91–114CrossRefPubMed
21.
Pan Z, Chen C, Long H, Lei C, Tang G, Li L, Feng J, Chen F (2013) Overexpression of GPC3 inhibits hepatocellular carcinoma cell proliferation and invasion through induction of apoptosis. Mol Med Rep 7(3):969–974PubMed
22.
Buchanan C, Stigliano I, Garay-Malpartida HM, Rodrigues Gomes L, Puricelli L, Sogayar MC, de Kier Bal, Joffe E, Peters MG (2010) Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3K/Akt and p38MAPK signaling pathways. Breast Cancer Res Treat 119(3):559–574CrossRefPubMed
23.
Jin M, Zhou X, Yearsley M, Frankel WL (2016) Liver Metastases of Neuroendocrine Tumors Rarely Show Overlapping Immunoprofile with Hepatocellular Carcinomas. Endocr Pathol 27(3):253–258CrossRefPubMed
24.
Chen L, Wu LL, Zhang ZL, Hu J, Tang M, Qi CB, Li N, Pang DW (2016) Biofunctionalized magnetic nanospheres-based cell sorting strategy for efficient isolation, detection and subtype analyses of heterogeneous circulating hepatocellular carcinoma cells. Biosens Bioelectron 85:633–640CrossRefPubMed
25.
Feng J, Zhu R, Chang C, Yu L, Cao F, Zhu G, Chen F, Xia H, Lv F, Zhang S, Sun L (2016) CK19 and glypican 3 expression profiling in the prognostic indication for patients with HCC after surgical resection. PLoS ONE 11(3):e0151501CrossRefPubMedPubMedCentral
26.
Tian Z, Jiang H, Liu Y, Huang Y, Xiong X, Wu H, Dai X (2016) MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1. Exp Cell Res 343(2):135–147CrossRefPubMed
27.
Abou-Alfa GK, Puig O, Daniele B, Kudo M, Merle P, Park JW, Ross P, Peron JM, Ebert O, Chan S, Poon TP, Colombo M, Okusaka T, Ryoo BY, Minguez B, Tanaka T, Ohtomo T, Ukrainskyj S, Boisserie F, Rutman O, Chen YC, Xu C, Shochat E, Jukofsky L, Reis B, Chen G, Di Laurenzio L, Lee R, Yen CJ (2016) Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma. J Hepatol 65(2):289–295CrossRefPubMed
28.
Aviel-Ronen S, Lau SK, Pintilie M, Lau D, Liu N, Tsao MS, Jothy S (2008) Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma. Mod Pathol 21(7):817–825CrossRefPubMed
29.
Tsuta K, Tanabe Y, Yoshida A, Takahashi F, Maeshima AM, Asamura H, Tsuda H (2011) Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the Lung. J Thorac Oncol 6(7):1190–1199CrossRefPubMed
30.
Kim H, Xu GL, Borczuk AC, Busch S, Filmus J, Capurro M, Brody JS, Lange J, D’Armiento JM, Rothman PB, Powell CA (2003) The heparan sulfate proteoglycan GPC3 is a potential lung tumor suppressor. Am J Respir Cell Mol Biol 29(6):694–701CrossRefPubMed
31.
Cai Y, Zou Z, Liu L, Chen S, Chen Y, Lin Z, Shi K, Xu L, Chen Y (2015) Bone marrow-derived mesenchymal stem cells inhibits hepatocyte apoptosis after acute liver injury. Int J Clin Exp Pathol 8(1):107–116PubMedPubMedCentral
32.
Capurro MI, Xiang YY, Lobe C, Filmus J (2005) Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. Cancer Res 65(14):6245–6254CrossRefPubMed
33.
Stigliano I, Puricelli L, Filmus J, Sogayar MC, de Kier Bal, Joffe E, Peters MG (2009) Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation. Breast Cancer Res Treat 114(2):251–262CrossRefPubMed
34.
Capurro M, Martin T, Shi W, Filmus J (2014) Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling. J Cell Sci 127(Pt 7):1565–1575CrossRefPubMed
35.
Cai SX, Liu AR, Chen S, He HL, Chen QH, Xu JY, Pan C, Yang Y, Guo FM, Huang YZ, Liu L, Qiu HB (2015) Activation of Wnt/beta-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice. Stem Cell Res Ther 6:65CrossRefPubMedPubMedCentral
36.
Lee CY, Yang JJ, Lee SS, Chen CJ, Huang YC, Huang KH, Kuan YH (2014) Protective effect of Ginkgo biloba leaves extract, EGb761, on endotoxin-induced acute lung injury via a JNK- and Akt-dependent NFkappaB pathway. J Agric Food Chem 62(27):6337–6344CrossRefPubMed
Metadata
Title
Can glypican-3 be a disease-specific biomarker?
Authors
Chaolei Chen
Xiaomin Huang
Zhaojian Ying
Dengmin Wu
Yani Yu
Xiangdong Wang
Chengshui Chen
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical and Translational Medicine / Issue 1/2017
Electronic ISSN: 2001-1326
DOI
https://doi.org/10.1186/s40169-017-0146-5

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