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

被引:53
作者
Espelt, Maria V.
Croci, Diego O. [2 ,3 ]
Bacigalupo, Maria L.
Carabias, Pablo
Manzi, Malena
Elola, Maria T.
Munoz, Marina C.
Dominici, Fernando P.
Wolfenstein-Todel, Carlota
Rabinovich, Gabriel A. [2 ,3 ]
Troncoso, Maria F. [1 ]
机构
[1] Univ Buenos Aires, Fac Farm & Bioquim, IQUIFIB, CONICET,Dept Quim Biol,Inst Quim & Fis Quim Biol, RA-1113 Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Inst Biol & Med Expt, Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina
[3] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, Buenos Aires, DF, Argentina
关键词
EPITHELIAL-CELLS; INTEGRINS; EXPRESSION; RECEPTORS; POLARITY; CANCER; FIBRONECTIN; TRAFFICKING; INVOLVEMENT; INDUCTION;
D O I
10.1002/hep.24294
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Galectin-1 (Gal-1), a widely expressed beta-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. (HEPATOLOGY 2011;53:2097-2106)
引用
收藏
页码:2097 / 2106
页数:10
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