Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties.
Galectin-3 is a carbohydrate-binding protein endowed with affinity for beta-galactosides. It plays a role in cell-cell and cell-matrix interactions. Furthermore, it has been hypothesized to be involved in tumor progression and metastasis. To address the role of galectin-3 in the invasive and metastatic processes, we stably overexpressed galectin-3 in human breast carcinoma cell lines, and we evaluated the influence of elevated galectin-3 expression on several cell features, including cellular homotypic and heterotypic interactions and cell survival. No differences in various parameters related with cell growth features and proliferation were detected. By contrast, we found that galectin-3 overexpressing cells, with respect to low galectin-3 expressing cells, exerted: (1) a significantly enhanced adhesion to laminin, fibronectin and vitronectin exerted both directly or via increased expression of specific integrins, e.g., alpha-4 and beta-7; (2) a remodeling of those cytoskeletal elements associated with cell spreading, i.e., microfilaments; (3) an enhanced survival upon exposure to different apoptotic stimuli, such as cytokine and radiation. Collectively, our results indicate that overexpression of galectin-3 may play a role in tumor cell invasion and metastasis by specifically influencing cell adhesion to the extracellular matrix. This may confer selective survival advantage and resistance to the particular homeless-induced apoptosis called anoikia.
Matarrese
P
P
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Fusco
O
O
Tinari
N
N
Natoli
C
C
Liu
F T
FT
Semeraro
M L
ML
Malorni
W
W
Iacobelli
S
S
D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005260:Female; D037502:Galectin 3; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D016207:Cytokines; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D037502:Galectin 3; D016023:Integrins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins