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.

Galectin-1 is essential for efficient liver regeneration following hepatectomy

“…The endogenous lectin Gal1 is mainly known for its regulatory role in the regulation of immune cell programs, inflammatory responses and angiogenesis; however it has also been implicated in the control of cell survival, signaling and proliferation, acting in different model systems either as a mitogen or as an inhibitor of cell proliferation [1, 11]. Here we identified a novel role for Gal1 in LR following PHx.…”

“…Expression of Gal1 is associated with the aggressiveness of hepatocellular carcinoma (HCC) in mice [11], low survival of HCC patients [12], and poor prognosis in HCC following resection [13]. Interestingly, Gal1 acts by promoting HCC cell adhesion through PI3K and/or ERK1/2 signaling pathways [14].…”

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

“…Lectin interactions with endogenous glycans control cell signaling and neovascularization [96, 203] and, therefore, can provide important information about hypoxic environments. When performing in vitro studies, Croci and Rabinovich (2014) observed that serum-free conditioned medium from an anti-VEGF refractory, but not anti-VEGF sensitive tumors, induced endothelial cell exposure of Gal-1-specific ligands.…”

Impact of Exogenous Galectin-9 on Human T Cells

“…Most often, these di-saccharides are part of complex glycans carried by glycoproteins or glycolipids (1). The domains of galectins that directly interact with carbohydrate ligands are carbohydrate recognition domains (CRD) 4 (2). The CRDs are made of about 135 amino acids forming a groove in which the carbohydrate ligand can bind.…”