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: Expression of MMP-9 on BSA-, fibronectin-, and LAP-coated tissue culture plastic was examined by zymography. Zymography on supernatant samples from cells grown in serum-free medium showed that the cells produced predominantly MMP-9 and that this enzyme was mainly present in proenzyme form. Similar to the effect observed on fibronectin (Thomas et al, 2001c), VB6 cells showed significant upregulation of MMP-9 when plated on LAP (P=<0.001; Figure 4A,CFigure 4
Affiliation: Department of Oral Pathology, Eastman Dental Institute, University College London, UK.