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Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.

Caffarel MM, Chattopadhyay A, Araujo AM, Bauer J, Scarpini CG, Coleman N - J. Pathol. (2013)

Bottom Line: Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness.Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells.We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, UK.

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Integrin–α5β1 expression in cervical SCC cells. (A) Western blot analysis of total levels of integrin–α5 (ITGA5) and integrin–β1 (ITGB1) in SW756 and CaSki, comparing OSM-treated cells (OSM) with control cells treated with vehicle only (C); β-actin (lower row) was used as the loading control. (B) Flow-cytometric measurement of cell surface integrin–α5β1 in SW756 and CaSki cells, comparing cells treated with OSM for 48 h (OSM) with control cells treated with vehicle only (C). Negative control cells were stained with an isotype control IgG. In the graphs (bottom row) statistical comparisons were between OSM-treated and control-treated cells: **p < 0.01; ***p < 0.001
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fig03: Integrin–α5β1 expression in cervical SCC cells. (A) Western blot analysis of total levels of integrin–α5 (ITGA5) and integrin–β1 (ITGB1) in SW756 and CaSki, comparing OSM-treated cells (OSM) with control cells treated with vehicle only (C); β-actin (lower row) was used as the loading control. (B) Flow-cytometric measurement of cell surface integrin–α5β1 in SW756 and CaSki cells, comparing cells treated with OSM for 48 h (OSM) with control cells treated with vehicle only (C). Negative control cells were stained with an isotype control IgG. In the graphs (bottom row) statistical comparisons were between OSM-treated and control-treated cells: **p < 0.01; ***p < 0.001

Mentions: Another of the 15 genes that were induced by OSM in OSMR-over-expressing cervical SCC cells, and also associated with OSMR over-expression in cervical SCC tissues 6, was integrin–α5 (ITGA5). As TGM2 has been reported to interact with integrin–α5β1 in mesenchymal cells, leading to binding of the cognate ligand fibronectin 23,24, we examined interactions between OSMR, TGM2, integrin–α5β1 and fibronectin in cervical SCC cells. OSM increased integrin–α5 (ITGA5), integrin–β1 (ITGB1) and fibronectin (FN1) mRNA levels in both SW756 and CaSki (see Supplementary material, Figure S2). After 48 h of OSM treatment, integrin–α5 protein levels increased 7.1- and 2.9-fold for SW756 and CaSki, respectively (Figure 3A). Integrin–β1 protein expression was also induced by OSM in CaSki, with a 1.5-fold increase at 48 h. Basal levels of integrin–β1 protein in SW756 were very high and expression did not increase further upon OSM treatment (Figure 3A). In the OSMR non-over-expressing cervical SCC cells MS751 and ME180, OSM did not induce integrin–α5 or integrin–β1 (see Supplementary material, Figure S3).


Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.

Caffarel MM, Chattopadhyay A, Araujo AM, Bauer J, Scarpini CG, Coleman N - J. Pathol. (2013)

Integrin–α5β1 expression in cervical SCC cells. (A) Western blot analysis of total levels of integrin–α5 (ITGA5) and integrin–β1 (ITGB1) in SW756 and CaSki, comparing OSM-treated cells (OSM) with control cells treated with vehicle only (C); β-actin (lower row) was used as the loading control. (B) Flow-cytometric measurement of cell surface integrin–α5β1 in SW756 and CaSki cells, comparing cells treated with OSM for 48 h (OSM) with control cells treated with vehicle only (C). Negative control cells were stained with an isotype control IgG. In the graphs (bottom row) statistical comparisons were between OSM-treated and control-treated cells: **p < 0.01; ***p < 0.001
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig03: Integrin–α5β1 expression in cervical SCC cells. (A) Western blot analysis of total levels of integrin–α5 (ITGA5) and integrin–β1 (ITGB1) in SW756 and CaSki, comparing OSM-treated cells (OSM) with control cells treated with vehicle only (C); β-actin (lower row) was used as the loading control. (B) Flow-cytometric measurement of cell surface integrin–α5β1 in SW756 and CaSki cells, comparing cells treated with OSM for 48 h (OSM) with control cells treated with vehicle only (C). Negative control cells were stained with an isotype control IgG. In the graphs (bottom row) statistical comparisons were between OSM-treated and control-treated cells: **p < 0.01; ***p < 0.001
Mentions: Another of the 15 genes that were induced by OSM in OSMR-over-expressing cervical SCC cells, and also associated with OSMR over-expression in cervical SCC tissues 6, was integrin–α5 (ITGA5). As TGM2 has been reported to interact with integrin–α5β1 in mesenchymal cells, leading to binding of the cognate ligand fibronectin 23,24, we examined interactions between OSMR, TGM2, integrin–α5β1 and fibronectin in cervical SCC cells. OSM increased integrin–α5 (ITGA5), integrin–β1 (ITGB1) and fibronectin (FN1) mRNA levels in both SW756 and CaSki (see Supplementary material, Figure S2). After 48 h of OSM treatment, integrin–α5 protein levels increased 7.1- and 2.9-fold for SW756 and CaSki, respectively (Figure 3A). Integrin–β1 protein expression was also induced by OSM in CaSki, with a 1.5-fold increase at 48 h. Basal levels of integrin–β1 protein in SW756 were very high and expression did not increase further upon OSM treatment (Figure 3A). In the OSMR non-over-expressing cervical SCC cells MS751 and ME180, OSM did not induce integrin–α5 or integrin–β1 (see Supplementary material, Figure S3).

Bottom Line: Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased cell migration and invasiveness.Here, we show that tissue transglutaminase (TGM2) is an important mediator of the ligand-dependent phenotypic effects of OSMR over-expression in SCC cells.We conclude that an OSMR/TGM2/integrin-α5β1/fibronectin pathway is of biological significance in cervical SCC and a candidate for therapeutic targeting.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, UK.

Show MeSH
Related in: MedlinePlus