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 M

HEPATOLOGY (BALTIMORE, MD.)

JOHN WILEY & SONS INC

Año: 2011 vol. 53 p. 2097 - 2106

0270-9139

Galectin-1 (Gal-1), a widely expressed b-galactoside–binding protein, exerts pleiotropic biologicalfunctions. Gal-1 is up-regulated in hepatocarcinoma cells, although its role inliver pathophysiology remains uncertain. We investigated the effects of Gal-1 on HepG2hepatocellular carcinoma (HCC) cell adhesion and polarization. Soluble and immobilizedrecombinant Gal-1 (rGal-1) promoted HepG2 cell adhesion to uncoated plates and alsoincreased adhesion to laminin. Antibody-mediated blockade experiments revealed theinvolvement of different integrins as critical mediators of these biological effects. In addition,exposure to rGal-1 markedly accelerated the development of apical bile canaliculi asshown by TRITC-phalloidin labeling and immunostaining for multidrug resistance associated-protein 2 (MRP2). Notably, rGal-1 did not interfere with multidrug resistance protein1/P-glycoprotein or MRP2 apical localization, neither with transfer nor secretion of5-chloromethylfluorescein diacetate through MRP2. Stimulation of cell adhesion andpolarization by rGal-1 was abrogated in the presence of thiodigalactoside, a galectin-specificsugar, suggesting the involvement of protein–carbohydrate interactions in theseeffects. Additionally, Gal-1 effects were abrogated in the presence of wortmmanin,PD98059 or H89, suggesting involvement of phosphoinositide 3-kinase (PI3K), mitogenactivatedprotein kinase and cyclic adenosine monophosphate–dependent protein kinasesignaling pathways in these functions. Finally, expression levels of this endogenous lectincorrelated with HCC cell adhesion and polarization and up-regulation of Gal-1–favoredgrowth of hepatocarcinoma in vivo. Conclusion: Our results provide the first evidence of arole 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)