[HTML][HTML] Binding of TGF-β1 latency-associated peptide (LAP) to αvβ6 integrin modulates behaviour of squamous carcinoma cells

GJ Thomas, IR Hart, PM Speight, JF Marshall - British journal of cancer, 2002 - nature.com
British journal of cancer, 2002nature.com
The integrin αvβ6 is not detectable on normal keratinocytes in vivo but expression is
increased significantly in oral squamous cell carcinoma where this heterodimer has been
shown to play a role in cell migration, invasion and protease expression. Although regarded
initially as a fibronectin receptor, αvβ6 may bind to arginine-glycine-aspartic acid sequences
in other matrix molecules including tenascin and vitronectin. Interestingly, αvβ6 has also
been shown to have high affinity for the TGF-β1 latency associated peptide and to …
Abstract
The integrin αvβ6 is not detectable on normal keratinocytes in vivo but expression is increased significantly in oral squamous cell carcinoma where this heterodimer has been shown to play a role in cell migration, invasion and protease expression. Although regarded initially as a fibronectin receptor, αvβ6 may bind to arginine-glycine-aspartic acid sequences in other matrix molecules including tenascin and vitronectin. Interestingly, αvβ6 has also been shown to have high affinity for the TGF-β1 latency associated peptide and to participate in the activation of the TGF-β1 latent complex. Since TGF-β1 is present in squamous carcinomas, it is possible that latency associated peptide may modulate malignant keratinocyte behaviour independently from the classical TGF-β signalling pathways through its interaction with integrins. We show here that when latency associated peptide is immobilised onto a surface, it acts as an αvβ6-specific ligand for oral squamous carcinoma cells promoting adhesion and haptotactic migration in addition to αvβ6-dependent increase in pro-MMP-9 expression. In contrast, even very low concentrations of soluble latency associated peptide (0.1 μg ml− 1) inhibited αvβ6-dependent adhesion, migration and invasion. Thus αvβ6-dependent processes of oral squamous cell carcinoma, is likely to be modulated, not only by the local concentration of latency associated peptide in the stroma, but also whether it is immobilised in the matrix or released as a soluble protein.
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