Binding of TGF-beta1 latency-associated peptide (LAP) to alpha(v)beta6 integrin modulates behaviour of squamous carcinoma cells.
Bottom Line: Since TGF-beta1 is present in squamous carcinomas, it is possible that latency associated peptide may modulate malignant keratinocyte behaviour independently from the classical TGF-beta signalling pathways through its interaction with integrins.We show here that when latency associated peptide is immobilised onto a surface, it acts as an alpha(v)beta6-specific ligand for oral squamous carcinoma cells promoting adhesion and haptotactic migration in addition to alpha(v)beta6-dependent increase in pro-MMP-9 expression.In contrast, even very low concentrations of soluble latency associated peptide (0.1 microg ml(-1)) inhibited alpha(v)beta6-dependent adhesion, migration and invasion.
Affiliation: Department of Oral Pathology, Eastman Dental Institute, University College London, UK.Show MeSH
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Mentions: VB6 cells bind to fibronectin through both αvβ6 and α5β1 integrins such that to completely inhibit adhesion to this substrate, a combination of blocking antibodies against both integrins is required (Thomas et al, 2001b). To determine whether LAP competitively inhibits αvβ6-dependent binding to fibronectin, VB6 cells were incubated with LAP (0.25 μg ml−1) or antibodies against αvβ6 (10D5) or α5β1 (P1D6) prior to plating. Treating the cells solely with LAP, or antibodies against αvβ6 or α5β1 did not inhibit adhesion to fibronectin significantly (Figure 5AFigure 5
Affiliation: Department of Oral Pathology, Eastman Dental Institute, University College London, UK.