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Binding of TGF-beta1 latency-associated peptide (LAP) to alpha(v)beta6 integrin modulates behaviour of squamous carcinoma cells.

Thomas GJ, Hart IR, Speight PM, Marshall JF - Br. J. Cancer (2002)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, Eastman Dental Institute, University College London, UK.

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Cell migration towards LAP is αvβ6-dependent. Cells were allowed to migrate towards LAP in haptotactic migration assays. To assess integrin specificity of migration, integrin-blocking antibodies against αv (L230), αvβ5 (P1F6), αvβ6 (10D5), or a control antibody (W632) were added to VB6, C1 and H357 cells prior to plating into wells. Following 8 h incubation, the cells in the lower chamber (including those attached to the undersurface of the membrane) were trypsinised and counted on a Casy 1 counter (Sharfe System GmbH, Germany). Results for the cell lines are expressed relative to VB6 migration following incubation with an irrelevant control antibody (=100). Figures show representative experiments performed in quadruplicate. Error bars represent standard deviation. (A) VB6 cells show increased migration towards LAP. Comparison of migration of VB6, C1 and H357 cells towards LAP. Migration is higher in the αvβ6 expressing VB6 cells. αv-negative H357 cells did not migrate significantly. (B) Migration towards LAP is αvβ6-dependent. Migration of VB6 and C1 cells was inhibited completely by antibody inhibition of αvβ6 or αv. Antibodies inhibiting αvβ5 produced no effect. These data suggest that migration of VB6 and C1 cells is modulated solely through αvβ6.
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fig3: Cell migration towards LAP is αvβ6-dependent. Cells were allowed to migrate towards LAP in haptotactic migration assays. To assess integrin specificity of migration, integrin-blocking antibodies against αv (L230), αvβ5 (P1F6), αvβ6 (10D5), or a control antibody (W632) were added to VB6, C1 and H357 cells prior to plating into wells. Following 8 h incubation, the cells in the lower chamber (including those attached to the undersurface of the membrane) were trypsinised and counted on a Casy 1 counter (Sharfe System GmbH, Germany). Results for the cell lines are expressed relative to VB6 migration following incubation with an irrelevant control antibody (=100). Figures show representative experiments performed in quadruplicate. Error bars represent standard deviation. (A) VB6 cells show increased migration towards LAP. Comparison of migration of VB6, C1 and H357 cells towards LAP. Migration is higher in the αvβ6 expressing VB6 cells. αv-negative H357 cells did not migrate significantly. (B) Migration towards LAP is αvβ6-dependent. Migration of VB6 and C1 cells was inhibited completely by antibody inhibition of αvβ6 or αv. Antibodies inhibiting αvβ5 produced no effect. These data suggest that migration of VB6 and C1 cells is modulated solely through αvβ6.

Mentions: VB6 cells show increased αvβ6-dependent migration towards fibronectin relative to the other cell lines (Thomas et al, 2001b). To determine whether VB6 cells migrated towards LAP, haptotactic migration assays were performed using LAP-coated Transwell filters. VB6 cells migrated less well towards LAP than fibronectin (a relative reduction of 53% over four experiments; P=0.039; data not shown). However, migration towards LAP was increased significantly in VB6 cells compared with C1 cells (P=<0.001; (Figure 3AFigure 3


Binding of TGF-beta1 latency-associated peptide (LAP) to alpha(v)beta6 integrin modulates behaviour of squamous carcinoma cells.

Thomas GJ, Hart IR, Speight PM, Marshall JF - Br. J. Cancer (2002)

Cell migration towards LAP is αvβ6-dependent. Cells were allowed to migrate towards LAP in haptotactic migration assays. To assess integrin specificity of migration, integrin-blocking antibodies against αv (L230), αvβ5 (P1F6), αvβ6 (10D5), or a control antibody (W632) were added to VB6, C1 and H357 cells prior to plating into wells. Following 8 h incubation, the cells in the lower chamber (including those attached to the undersurface of the membrane) were trypsinised and counted on a Casy 1 counter (Sharfe System GmbH, Germany). Results for the cell lines are expressed relative to VB6 migration following incubation with an irrelevant control antibody (=100). Figures show representative experiments performed in quadruplicate. Error bars represent standard deviation. (A) VB6 cells show increased migration towards LAP. Comparison of migration of VB6, C1 and H357 cells towards LAP. Migration is higher in the αvβ6 expressing VB6 cells. αv-negative H357 cells did not migrate significantly. (B) Migration towards LAP is αvβ6-dependent. Migration of VB6 and C1 cells was inhibited completely by antibody inhibition of αvβ6 or αv. Antibodies inhibiting αvβ5 produced no effect. These data suggest that migration of VB6 and C1 cells is modulated solely through αvβ6.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376166&req=5

fig3: Cell migration towards LAP is αvβ6-dependent. Cells were allowed to migrate towards LAP in haptotactic migration assays. To assess integrin specificity of migration, integrin-blocking antibodies against αv (L230), αvβ5 (P1F6), αvβ6 (10D5), or a control antibody (W632) were added to VB6, C1 and H357 cells prior to plating into wells. Following 8 h incubation, the cells in the lower chamber (including those attached to the undersurface of the membrane) were trypsinised and counted on a Casy 1 counter (Sharfe System GmbH, Germany). Results for the cell lines are expressed relative to VB6 migration following incubation with an irrelevant control antibody (=100). Figures show representative experiments performed in quadruplicate. Error bars represent standard deviation. (A) VB6 cells show increased migration towards LAP. Comparison of migration of VB6, C1 and H357 cells towards LAP. Migration is higher in the αvβ6 expressing VB6 cells. αv-negative H357 cells did not migrate significantly. (B) Migration towards LAP is αvβ6-dependent. Migration of VB6 and C1 cells was inhibited completely by antibody inhibition of αvβ6 or αv. Antibodies inhibiting αvβ5 produced no effect. These data suggest that migration of VB6 and C1 cells is modulated solely through αvβ6.
Mentions: VB6 cells show increased αvβ6-dependent migration towards fibronectin relative to the other cell lines (Thomas et al, 2001b). To determine whether VB6 cells migrated towards LAP, haptotactic migration assays were performed using LAP-coated Transwell filters. VB6 cells migrated less well towards LAP than fibronectin (a relative reduction of 53% over four experiments; P=0.039; data not shown). However, migration towards LAP was increased significantly in VB6 cells compared with C1 cells (P=<0.001; (Figure 3AFigure 3

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, Eastman Dental Institute, University College London, UK.

Show MeSH
Related in: MedlinePlus