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

The integrin alphanubeta6 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, alphanubeta6 may bind to arginine-glycine-aspartic acid sequences in other matrix molecules including tenascin and vitronectin. Interestingly, alphanubeta6 has also been shown to have high affinity for the TGF-beta1 latency associated pepticle and to participate in the activation of the TGF-beta1 latent complex. Since TGF-beta1 is present in squamous carcinomas, it is possible that latency associated pepticle 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 pepticle is immobilised onto a surface, it acts as an alphanubeta6-specific ligand for oral squamous carcinoma cells promoting adhesion and haptotactic migration in addition to alphanubeta6-dependent increase in pro-MMP-9 expression. In contrast, even very low concentrations of soluble latency associated pepticle (0.1 mug ml(-1)) inhibited alphanubeta6-dependent adhesion, migration and invasion, Thus alphanubeta6-dependent processes of oral squamous cell carcinoma, is likely to be modulated, not only by the local concentration of latency associated pepticle in the stroma, but also whether it is immobilised in the matrix or released as a soluble protein. (C) 2002 Cancer Research UK.