The Role of Oncostatin M Receptor Over-Expression in Tumour Microenvironment of Cervical Squamous Cell Carcinoma

An important feature of cervical squamous carcinogenesis is genomic instability caused by deregulated expression of human papillomavirus oncogenes in proliferating epithelial cells. One common change is gain of the region of chromosome 5p that encodes, amongst others, the Oncostatin-M receptor (OSMR; located at 5p13.1). OSMR is often over-expressed in cervical SCC and this over-expression is associated with a significantly worse clinical outcome (1). Cervical SCC cells that over-express OSMR show enhanced responsiveness to its major ligand Oncostatin-M (OSM), which in turn, mediates multiple pro-malignant effects, including a pro-angiogenic phenotype and increased cell migration and invasiveness (2). Furthermore, OSM induces expression of genes associated with hypoxia, epithelial to mesenchymal transition, metastasis and immune cell recruitment (2). In vivo, OSM promotes lung colonisation and growth of OSMR over-expressing cervical SCC cells in mouse xenografts (unpublished data). We are currently studying the effects of OSMR over-expression on the SCC tumour microenvironment in vivo as well as the interactions between OSMR over-expressing cells and macrophages in vitro, to ultimately better understand the activation of pro-tumorigenic hypoxic responses and their role in immune cell recruitment, angiogenesis and epithelial to mesenchymal transition.

1. Ng G, et al (2007) Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome. Journal of Pathology 212:325-34.
2. Winder DM, et al (2011) Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness. Journal of Pathology 225:448-62
3. Caffarel MM, Coleman N. (2014) Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma. Journal of Pathology 232:386-90