Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.
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.
Affiliation: Department of Pathology, University of Cambridge, UK.Show MeSH
Related in: MedlinePlus
Mentions: In our previous study of sample set 1, TGM2 was significantly up-regulated in cervical SCC samples with OSMR over-expression, compared with those that lacked OSMR over-expression 6. There was no association between OSMR and TGM2 gene copy number in this sample set, as assessed by comparative genomic hybridization (data not shown). Using linear regression analysis, we found that levels of TGM2 mRNA correlated significantly with those of OSMR in all the set 1 SCC samples (n = 29; Figure 1A). The frequency of TGM2-positive cells, as determined by immunohistochemistry, was also significantly higher in sections of the 19 cervical SCC samples from set 2 that showed OSMR copy number gain, versus the 18 samples that lacked OSMR copy number gain (Figure 1B).
Affiliation: Department of Pathology, University of Cambridge, UK.