title: Galectin-1 Controls the Proliferation and Migration of Liver Sinusoidal Endothelial Cells and Their Interaction With Hepatocarcinoma Cells.
abstract: Galectin-1 (Gal1), a β-galactoside-binding protein elevated in hepatocellular carcinoma (HCC), promotes epithelial-mesenchymal transition (EMT) and its expression correlates with HCC growth, invasiveness, and metastasis. During the early stages of HCC, transforming growth factor β1 (TGF-β1 ) acts as a tumor suppressor; however in advanced stages, HCC cells lose their cytostatic response to TGF-β1 and undergo EMT. Here, we investigated the role of Gal1 on liver endothelial cell biology, and the interplay between Gal1 and TGF-β1 in HCC progression. By Western blot and immunofluorescence, we analyzed Gal1 expression, secretion and localization in HepG2 and HuH-7 human HCC cells, and in SK-HEP-1 human liver sinusoidal endothelial cells (SECs). We used loss-of-function and gain-of-function experiments to down- or up-regulate Gal1 expression, respectively, in HepG2 cells. We cultured SK-HEP-1 cells with conditioned media from HCC cells secreting different levels of Gal1, and demonstrated that Gal1 derived from tumor hepatocytes induced its own expression in SECs. Colorimetric and scratch-wound assays revealed that secretion of Gal1 by HCC cells induced SEC proliferation and migration. Moreover, by fluorescence microscopy we demonstrated that Gal1 promoted glycan-dependent heterotypic adhesion of HepG2 cells to SK-HEP-1 SECs. Furthermore, TGF-β1 induced Gal1 expression and secretion by HCC cells, and promoted HepG2 cell adhesion to SK-HEP-1 SECs through a Gal1-dependent mechanism. Finally, Gal1 modulated HepG2 cell proliferation and sensitivity to TGF-β1 -induced growth inhibition. Our results suggest that Gal1 and TGF-β1 might function coordinately within the HCC microenvironment to regulate tumor growth, invasion, metastasis, and angiogenesis.
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: Malena
authors.initials: M
authors.lastname: Manzi
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: María L
authors.initials: ML
authors.lastname: Bacigalupo
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Carabias
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: María T
authors.initials: MT
authors.lastname: Elola
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: Carlota
authors.initials: C
authors.lastname: Wolfenstein-Todel
authors.affiliation: Institute of Biology and Experimental Medicine (CONICET) and School of Exact and Natural Sciences, University of Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Espelt
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Troncoso
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D042783:Endothelial Cells; D058750:Epithelial-Mesenchymal Transition; D037483:Galectin 1 / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*; D059016:Tumor Microenvironment
chemical_list: D037483:Galectin 1; D053773:Transforming Growth Factor beta1