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 ; RABINOVICH GA; TRONCOSO MF

HEPATOLOGY (BALTIMORE, MD.)

JOHN WILEY & SONS INC

Lugar: Baltimore; Año: 2011 vol. 53 p. 2097 - 2106

0270-9139

Galectin-1 (Gal-1), a widely expressed b-galactoside–binding protein, exerts pleiotropic bi- ological functions. Gal-1 is up-regulated in hepatocarcinoma cells, although its role in liver pathophysiology remains uncertain. 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 adhesion to laminin. Antibody-mediated blockade experiments revealed the involvement of different integrins as critical mediators of these biological effects. In addi- tion, exposure to rGal-1 markedly accelerated the development of apical bile canaliculi as shown by TRITC-phalloidin labeling and immunostaining for multidrug resistance associ- ated-protein 2 (MRP2). Notably, rGal-1 did not interfere with multidrug resistance pro- tein 1/P-glycoprotein or MRP2 apical localization, neither with transfer nor secretion of 5-chloromethylfluorescein diacetate through MRP2. Stimulation of cell adhesion and polarization by rGal-1 was abrogated in the presence of thiodigalactoside, a galectin-spe- cific sugar, suggesting the involvement of protein–carbohydrate interactions in these effects. Additionally, Gal-1 effects were abrogated in the presence of wortmmanin, PD98059 or H89, suggesting involvement of phosphoinositide 3-kinase (PI3K), mitogen- activated protein kinase and cyclic adenosine monophosphate–dependent protein kinase signaling pathways in these functions. Finally, expression levels of this endogenous lectin correlated with HCC cell adhesion and polarization and up-regulation of Gal-1–favored growth of hepatocarcinoma in vivo. 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. (HEPATOLOGY 2011;53:2097-2106)