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Novel roles of galectin‐1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
Author(s) -
Espelt María V.,
Croci Diego O.,
Bacigalupo María L.,
Carabias Pablo,
Manzi Malena,
Elola María T.,
Muñoz Marina C.,
Dominici Fernando P.,
WolfensteinTodel Carlota,
Rabinovich Gabriel A.,
Troncoso María F.
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24294
Subject(s) - galectin , microbiology and biotechnology , protein kinase a , cell adhesion , biology , protein kinase b , cancer research , integrin , cell growth , focal adhesion , signal transduction , chemistry , kinase , cell , biochemistry
Galectin‐1 (Gal‐1), a widely expressed β‐galactoside–binding protein, exerts pleiotropic biological 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 addition, exposure to rGal‐1 markedly accelerated the development of apical bile canaliculi 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 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‐specific 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. (H EPATOLOGY 2011;)