Novel Roles of Galectin-1 in Hepatocellular Carcinoma Cell Adhesion, Polarization and In Vivo Tumor Growth

ESPELT MV; CROCI DO; BACIGALUPO ML; CARABIAS P; MANZI M; ELOLA MT; MUÑOZ MC; DOMINICI FP; WOLFENSTEIN-TODEL C; RABINOVICH GA; TRONCOSO MF

HEPATOLOGY (BALTIMORE, MD.)

JOHN WILEY & SONS INC

Año: 2011 vol. 53 p. 2097 - 2106

0270-9139

Galectin-1 (Gal-1), a widely expressed â-galactoside-binding protein, exerts pleiotropic biological functions. Gal-1 is up-regulated in hepatocarcinoma cells, although its role in liver pathophysiology remains uncertain. Here we investigated the effects of Gal-1 on HepG2 hepatocellular carcinoma (HCC) cell adhesion and polarization. Soluble and immobilized recombinant Gal-1 (rGal-1) promoted HepG2 cell adhesion to uncoated plates and also increased cell adhesion to laminin. Antibody-mediated blockade experiments revealed the involvement of different integrins as primary mediators of these biological effects. In addition, exposure to rGal-1 markedly accelerated the development of apical bile canaliculi (BC) development as shown by TRITC-phalloidin labeling and immunostaining for multidrug resistance associated-protein 2 (MRP2). Notably, rGal-1 did not interfere with multidrug resistance protein 1/P-glycoprotein (MDR1) or MRP2 apical localization, neither with transfer and secretion of 5-chloromethylfluorescein diacetate (CMFDA) through MRP2. Stimulation of cell adhesion and polarization by rGal-1 was abrogated in the presence of thiodigalactoside, a galectin-specific sugar, suggesting the involvement of protein-carbohydrate interactions in these functions. Additionally, in the presence of wortmmanin, PD98059 or H89, Gal-1 effects were abrogated, suggesting involvement of phosphoinositide 3-kinase (PI3K), mitogen activated protein kinase (MAPK) and cAMP-dependent protein kinase (PKA) signaling pathways in these effects. Remarkably, expression levels of this endogenous lectin correlated with HCC cell adhesion and polarization. Interestingly, Gal-1 upregulation promoted in vivo tumor growth. Conclusion: Our results provide the first evidence of a role of Gal-1 in modulating HCC cell adhesion, polarization and in vivo tumor growth, with critical implications in liver pathophysiology.