Abstract
Expression of galectin-3 is associated with sarcoma progression, invasion and metastasis. Here we determined the role of extracellular galectin-3 on migration of sarcoma cells on laminin-111. Cell lines from methylcholanthrene-induced sarcomas from both wild type and galectin-3−/− mice were established. Despite the presence of similar levels of laminin-binding integrins on the cell surface, galectin-3−/− sarcoma cells were more adherent and less migratory than galectin-3+/+ sarcoma cells on laminin-111. When galectin-3 was transiently expressed in galectin-3−/− sarcoma cells, it inhibited cell adhesion and stimulated the migratory response to laminin in a carbohydrate-dependent manner. Extracellular galectin-3 led to the recruitment of SHP-2 phosphatase to focal adhesion plaques, followed by a decrease in the amount of phosphorylated FAK and phospho-paxillin in the lamellipodia of migrating cells. The promigratory activity of extracellular galectin-3 was inhibitable by wortmannin, implicating the activation of a PI-3 kinase dependent pathway in the galectin-3 triggered disruption of adhesion plaques, leading to sarcoma cell migration on laminin-111.
Highlights
Activation of the migratory and invasive capacities by tumor cells are often associated with tumor progression [1]
Cytoplasmic galectin-3 is recruited to the leading edge of migrating cells
Modulation of migration was associated with the recruitment of Shp2 tyrosine phosphatase to focal complexes and an apparent acceleration of FAK and paxillin turnover on focal contacts, as evaluated by the decrease of phosphorylated-FAK in lamellipodia of migrating cells and paxillin in focal complexs
Summary
Activation of the migratory and invasive capacities by tumor cells are often associated with tumor progression [1]. Central to these changes are alterations in either the expression pattern or activity of integrins, key regulators of the organization of cytoskeleton, cell adhesion and survival [2]. Migration on laminin is considered a dysfunctional pattern of migration for fibroblasts [5] We showed that this pattern was dependent on the expression of a6b1 integrin, whose expression is up-regulated after transfection with activated ras. These N-linked glycans may present polylactosamine structures, which are among the glycans recognized by the animal lectin, galectin-3 [10,11,12]
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