title: Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma.
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.
authors.affiliation: 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.
authors.forename: María L
authors.initials: ML
authors.lastname: Bacigalupo
authors.affiliation: 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.
authors.forename: Malena
authors.initials: M
authors.lastname: Manzi
authors.affiliation: 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.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: 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.
authors.forename: María F
authors.initials: MF
authors.lastname: Troncoso
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D015195:Drug Design; D037161:Galectins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006505:Hepatitis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D037161:Galectins
keywords: Fibrosis-related liver pathologies; Galectins; Hepatitis B or C virus infection-associated hepatocellular carcinoma; Hepatocellular carcinoma; Inflammation-associated liver injury