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Binding of TGF- ?1 latency-associated peptide (LAP) to ???6 integrin modulates behaviour of squamous carcinoma cells

Binding of TGF- ?1 latency-associated peptide (LAP) to ???6 integrin modulates behaviour of squamous carcinoma cells
Binding of TGF- ?1 latency-associated peptide (LAP) to ???6 integrin modulates behaviour of squamous carcinoma cells
The integrin ?v?6 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, ?v?6 may bind to arginine-glycine-aspartic acid sequences in other matrix molecules including tenascin and vitronectin. Interestingly, ?v?6 has also been shown to have high affinity for the TGF-1 latency associated peptide and to participate in the activation of the TGF-1 latent complex. Since TGF-1 is present in squamous carcinomas, it is possible that latency associated peptide may modulate malignant keratinocyte behaviour independently from the classical TGF- signalling pathways through its interaction with integrins. We show here that when latency associated peptide is immobilised onto a surface, it acts as an ?v?6-specific ligand for oral squamous carcinoma cells promoting adhesion and haptotactic migration in addition to ?v?6-dependent increase in pro-MMP-9 expression. In contrast, even very low concentrations of soluble latency associated peptide (0.1 g ml-1) inhibited ?v?6-dependent adhesion, migration and invasion. Thus ?v?6-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.
integrins, squamous carcinoma, MMP-9, TGF- ?1, LAP, adhesion, migration, invasion
0007-0920
859-867
Thomas, G.J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Hart, I.R.
7bfb93f0-86c5-4200-af57-fd7f251076c1
Speight, P.M.
e5e8d0a3-c9d8-4054-aa9e-c6a186c48e9f
Marshall, J.F.
0f31dde6-5c31-4070-9c54-2e2f59711014
Thomas, G.J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Hart, I.R.
7bfb93f0-86c5-4200-af57-fd7f251076c1
Speight, P.M.
e5e8d0a3-c9d8-4054-aa9e-c6a186c48e9f
Marshall, J.F.
0f31dde6-5c31-4070-9c54-2e2f59711014

Thomas, G.J., Hart, I.R., Speight, P.M. and Marshall, J.F. (2002) Binding of TGF- ?1 latency-associated peptide (LAP) to ???6 integrin modulates behaviour of squamous carcinoma cells. British Journal of Cancer, 87 (8), 859-867. (doi:10.1038/sj.bjc.6600545).

Record type: Article

Abstract

The integrin ?v?6 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, ?v?6 may bind to arginine-glycine-aspartic acid sequences in other matrix molecules including tenascin and vitronectin. Interestingly, ?v?6 has also been shown to have high affinity for the TGF-1 latency associated peptide and to participate in the activation of the TGF-1 latent complex. Since TGF-1 is present in squamous carcinomas, it is possible that latency associated peptide may modulate malignant keratinocyte behaviour independently from the classical TGF- signalling pathways through its interaction with integrins. We show here that when latency associated peptide is immobilised onto a surface, it acts as an ?v?6-specific ligand for oral squamous carcinoma cells promoting adhesion and haptotactic migration in addition to ?v?6-dependent increase in pro-MMP-9 expression. In contrast, even very low concentrations of soluble latency associated peptide (0.1 g ml-1) inhibited ?v?6-dependent adhesion, migration and invasion. Thus ?v?6-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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Published date: October 2002
Keywords: integrins, squamous carcinoma, MMP-9, TGF- ?1, LAP, adhesion, migration, invasion

Identifiers

Local EPrints ID: 66692
URI: http://eprints.soton.ac.uk/id/eprint/66692
ISSN: 0007-0920
PURE UUID: 1059c26f-8f0a-4958-b89d-17e2e1d733d5

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Date deposited: 10 Jul 2009
Last modified: 30 Jul 2019 19:12

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Contributors

Author: G.J. Thomas
Author: I.R. Hart
Author: P.M. Speight
Author: J.F. Marshall

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