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World J Gastroenterol. Dec 21, 2013; 19(47): 8831-8849
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.8831
Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma
María L Bacigalupo, Malena Manzi, Gabriel A Rabinovich, María F Troncoso
María L Bacigalupo, Malena Manzi, María F Troncoso, Institute of Biological Chemistry and Biophysics “Prof. Alejandro C. Paladini” (UBA-CONICET), Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD, Buenos Aires, Argentina
Gabriel A Rabinovich, Institute of Biology and Experimental Medicine (CONICET), Department of Biological Chemistry, School of Exact and Natural Sciences, University of Buenos Aires, C1113AAD Buenos Aires, Argentina
Author contributions: Bacigalupo ML and Manzi M contributed to manuscript writing, final revision of the article and figure composing; Rabinovich GA critically revised the manuscript for important intellectual content; Troncoso MF contributed to the study idea and design, literature search, figure composing, manuscript writing and, final revision of the article.
Correspondence to: María Fernanda Troncoso, PhD, Institute of Biological Chemistry and Biophysics “Prof. Alejandro C. Paladini” (UBA-CONICET), Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina. ma.f.troncoso@gmail.com
Telephone: +54-11-49648290 Fax: +54-11-49625457
Received: August 15, 2013
Revised: November 2, 2013
Accepted: November 18, 2013
Published online: December 21, 2013
Processing time: 111 Days and 19.2 Hours
Abstract

Hepatocellular carcinoma (HCC) represents a global health problem. Infections with hepatitis B or C virus, non-alcoholic steatohepatitis disease, alcohol abuse, or dietary exposure to aflatoxin are the major risk factors to the development of this tumor. Regardless of the carcinogenic insult, HCC usually develops in a context of cirrhosis due to chronic inflammation and advanced fibrosis. Galectins are a family of evolutionarily-conserved proteins defined by at least one carbohydrate recognition domain with affinity for β-galactosides and conserved sequence motifs. Here, we summarize the current literature implicating galectins in the pathogenesis of HCC. Expression of “proto-type” galectin-1, “chimera-type” galectin-3 and “tandem repeat-type” galectin-4 is up-regulated in HCC cells compared to their normal counterparts. On the other hand, the “tandem-repeat-type” lectins galectin-8 and galectin-9 are down-regulated in tumor hepatocytes. The abnormal expression of these galectins correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, postoperative recurrence and poor prognosis. Moreover, these galectins have important roles in other pathological conditions of the liver, where chronic inflammation and/or fibrosis take place. Galectin-based therapies have been proposed to attenuate liver pathologies. Further functional studies are required to delineate the precise molecular mechanisms through which galectins contribute to HCC.

Keywords: Galectins; Hepatocellular carcinoma; Inflammation-associated liver injury; Hepatitis B or C virus infection-associated hepatocellular carcinoma; Fibrosis-related liver pathologies

Core tip: Galectins, a family of glycan-binding proteins, are involved in the pathogenesis of hepatocellular carcinoma (HCC). Up-regulation of galectin-1, galectin-3 and galectin-4 is observed in HCC cells, whereas galectin-8 and galectin-9 appear to be down-regulated in tumor hepatocytes. This altered expression correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, postoperative recurrence and poor prognosis. These galectins are also implicated in inflammation- and fibrosis-related liver pathologies.