Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth

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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) ce...

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Autores principales:	Espelt, M.V., Croci, D.O., Bacigalupo, M.L., Carabias, P., Manzi, M., Elola, M.T., Muñoz, M.C., Dominici, F.P., Wolfenstein-Todel, C., Rabinovich, G.A., Troncoso, M.F.
Formato:	JOUR
Materias:	beta galactoside galectin 1 integrin laminin lectin multidrug resistance protein 2 phalloidin sugar thioglycoside article cell adhesion controlled study human human cell immunohistochemistry intrahepatic bile duct liver cell carcinoma pathophysiology pleiotropy priority journal protein localization tumor growth Carcinoma, Hepatocellular Cell Adhesion Cell Line, Tumor Cell Polarity Cell Proliferation Cyclic AMP-Dependent Protein Kinases Galectin 1 Humans Liver Neoplasms Mitogen-Activated Protein Kinases Multidrug Resistance-Associated Proteins Phosphatidylinositol 3-Kinases Signal Transduction
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_02709139_v53_n6_p2097_Espelt
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_02709139_v53_n6_p2097_Espelt
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spelling	todo:paper_02709139_v53_n6_p2097_Espelt2023-10-03T15:14:51Z Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth Espelt, M.V. Croci, D.O. Bacigalupo, M.L. Carabias, P. Manzi, M. Elola, M.T. Muñoz, M.C. Dominici, F.P. Wolfenstein-Todel, C. Rabinovich, G.A. Troncoso, M.F. beta galactoside galectin 1 integrin laminin lectin multidrug resistance protein 2 phalloidin sugar thioglycoside article cell adhesion controlled study human human cell immunohistochemistry intrahepatic bile duct liver cell carcinoma pathophysiology pleiotropy priority journal protein localization tumor growth Carcinoma, Hepatocellular Cell Adhesion Cell Line, Tumor Cell Polarity Cell Proliferation Cyclic AMP-Dependent Protein Kinases Galectin 1 Humans Liver Neoplasms Mitogen-Activated Protein Kinases Multidrug Resistance-Associated Proteins Phosphatidylinositol 3-Kinases Signal Transduction 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. Copyright © 2011 American Association for the Study of Liver Diseases. Fil:Espelt, M.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Croci, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Elola, M.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Troncoso, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02709139_v53_n6_p2097_Espelt
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	beta galactoside galectin 1 integrin laminin lectin multidrug resistance protein 2 phalloidin sugar thioglycoside article cell adhesion controlled study human human cell immunohistochemistry intrahepatic bile duct liver cell carcinoma pathophysiology pleiotropy priority journal protein localization tumor growth Carcinoma, Hepatocellular Cell Adhesion Cell Line, Tumor Cell Polarity Cell Proliferation Cyclic AMP-Dependent Protein Kinases Galectin 1 Humans Liver Neoplasms Mitogen-Activated Protein Kinases Multidrug Resistance-Associated Proteins Phosphatidylinositol 3-Kinases Signal Transduction
spellingShingle	beta galactoside galectin 1 integrin laminin lectin multidrug resistance protein 2 phalloidin sugar thioglycoside article cell adhesion controlled study human human cell immunohistochemistry intrahepatic bile duct liver cell carcinoma pathophysiology pleiotropy priority journal protein localization tumor growth Carcinoma, Hepatocellular Cell Adhesion Cell Line, Tumor Cell Polarity Cell Proliferation Cyclic AMP-Dependent Protein Kinases Galectin 1 Humans Liver Neoplasms Mitogen-Activated Protein Kinases Multidrug Resistance-Associated Proteins Phosphatidylinositol 3-Kinases Signal Transduction Espelt, M.V. Croci, D.O. Bacigalupo, M.L. Carabias, P. Manzi, M. Elola, M.T. Muñoz, M.C. Dominici, F.P. Wolfenstein-Todel, C. Rabinovich, G.A. Troncoso, M.F. Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
topic_facet	beta galactoside galectin 1 integrin laminin lectin multidrug resistance protein 2 phalloidin sugar thioglycoside article cell adhesion controlled study human human cell immunohistochemistry intrahepatic bile duct liver cell carcinoma pathophysiology pleiotropy priority journal protein localization tumor growth Carcinoma, Hepatocellular Cell Adhesion Cell Line, Tumor Cell Polarity Cell Proliferation Cyclic AMP-Dependent Protein Kinases Galectin 1 Humans Liver Neoplasms Mitogen-Activated Protein Kinases Multidrug Resistance-Associated Proteins Phosphatidylinositol 3-Kinases Signal Transduction
description	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. Copyright © 2011 American Association for the Study of Liver Diseases.
format	JOUR
author	Espelt, M.V. Croci, D.O. Bacigalupo, M.L. Carabias, P. Manzi, M. Elola, M.T. Muñoz, M.C. Dominici, F.P. Wolfenstein-Todel, C. Rabinovich, G.A. Troncoso, M.F.
author_facet	Espelt, M.V. Croci, D.O. Bacigalupo, M.L. Carabias, P. Manzi, M. Elola, M.T. Muñoz, M.C. Dominici, F.P. Wolfenstein-Todel, C. Rabinovich, G.A. Troncoso, M.F.
author_sort	Espelt, M.V.
title	Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
title_short	Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
title_full	Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
title_fullStr	Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
title_full_unstemmed	Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
title_sort	novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth
url	http://hdl.handle.net/20.500.12110/paper_02709139_v53_n6_p2097_Espelt
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Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth

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