Overexpression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survival.

Abstract

BACKGROUND:

Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical squamous cell carcinoma (SCC) and is associated with adverse clinical outcome. We previously showed that OSMR overexpression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases migration and invasion in vitro. We hypothesised that a major contribution to this phenotype would come from epithelial-mesenchymal transition (EMT).

METHODS:

We performed a comprehensive integrated study, involving in vitro cell line studies, in vivo animal models and numerous clinical samples from a variety of anatomical sites.

RESULTS:

In independent sets of cervical, head/neck and lung SCC tissues, OSMR expression levels correlated with multiple EMT-associated phenotypic markers and transcription factors. OSM treatment of OSMR overexpressing cervical SCC cells produced consistent EMT changes and increased tumour sphere formation in suspension culture. In a mouse model, OSMR overexpressing SCC cells treated with OSM showed significant increases in lung colonisation. The biological effects of exogenous OSM were mirrored by highly significant adverse overall survival in cervical SCCs with OSMR overexpression (N=251).

CONCLUSIONS:

OSM:OSMR interactions are able to induce EMT, increased cancer stem cell-like properties and enhanced lung colonisation in SCC cells. These changes are likely to contribute to the highly significant adverse outcome associated with OSMR overexpression in cervical SCCs.

• Authors: Justyna A Kucia-Tran, Valtteri Tulkki, Stephen Smith, Cinzia G Scarpini, Katherine Hughes, Angela M Araujo, Ka Yin Matthew Yan, Jan Botthof, Eduardo Pérez-Gómez, Miguel Quintanilla, Kate Cuschieri, Maria M Caffarel, Nicholas Coleman
• Journal: British journal of cancer (Br J Cancer) Vol. 115 Issue 2 Pg. 212-22 (07 12 2016) ISSN: 1532-1827 [Electronic] England
• PMID: 27351213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Oncostatin M
• STAT3 Transcription Factor
• STAT3 protein, human
• JAK2 protein, human
• Janus Kinase 2

Topics

• Animals
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition
• Female
• Heterografts
• Humans
• Janus Kinase 2 (metabolism)
• Mice
• Neoplasm Metastasis
• Receptors, Oncostatin M (metabolism)
• STAT3 Transcription Factor (metabolism)
• Survival Analysis
• Uterine Cervical Neoplasms (metabolism, pathology)