In:
Journal of Cell Science, The Company of Biologists, Vol. 113, No. 13 ( 2000-07-01), p. 2385-2397
Abstract:
The interaction of cells with the extracellular matrix regulates cell adhesion, motility, growth, survival and differentiation through integrinmediated signal transduction. Here we demonstrate that galectin-8, a secreted mammalian β-galactoside binding protein, inhibits adhesion of human carcinoma (1299) cells to plates coated with integrin ligands, and induces cell apoptosis. Pretreatment of the cells with Mn2+, which increases the affinity of integrins for their ligands, abolished the inhibitory effects of galectin-8. The inhibitory effects of galectin-8 were specific and were not mimicked by plant lectins or other galectins (galectin-1 and galectin-3). In accordance with its antiadhesive effects, transfection of galectin-8 cDNA into 1299 cells significantly reduced (by 75%) colony formation, when compared to the number of colonies formed by cells transfected with an empty vector. Affinity chromatography over immobilized galectin-8 indicated that few membrane proteins interacted with galectin-8 in a sugardependent manner. Microsequencing and western immunoblotting revealed that α3β1 integrin derived from 1299 as well as other cells (e.g. HeLa and human endothelial cells) is a major galectin-8 bindingprotein. Furthermore, immunoprecipitation and immunohistochemical studies suggested that endogenous galectin-8, secreted from 1299 cells, forms complexes with α3β1 integrins expressed on the surface of 1299 cells. Galectin-8 also interacts with other members of the integrin family, like α6β1 integrins. In contrast, galectin-8 only minimally interacts with α4 or β3 integrins. We propose that galectin-8 is an integrin bindingprotein that interacts to a different extent with several, but not all members of the integrin family. Binding of galectin-8 modulates integrin interactions with the extracellular matrix and thus regulates cell adhesion and cell survival.
Type of Medium:
Online Resource
ISSN:
0021-9533
,
1477-9137
DOI:
10.1242/jcs.113.13.2385
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2000
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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