title: Overexpression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survival.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Kucia-Tran
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Valtteri
authors.initials: V
authors.lastname: Tulkki
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Cinzia G
authors.initials: CG
authors.lastname: Scarpini
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Hughes
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Araujo
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Ka Yin Matthew
authors.initials: KY
authors.lastname: Yan
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Botthof
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid 28040, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pérez-Gómez
authors.affiliation: Department of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid 28029, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintanilla
authors.affiliation: Scottish Human Papilloma Virus Reference Laboratory, Specialist Virology Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Cuschieri
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Caffarel
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Coleman
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D064593:Heterografts; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D053677:Receptors, Oncostatin M / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D053677:Receptors, Oncostatin M; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2