10.17863/CAM.408
Kucia-Tran, Justyna A
Tulkki, Valtteri
Smith, Stephen
0000-0001-7744-3238
Scarpini, Cinzia
0000-0003-4730-5197
Hughes, Katherine
0000-0002-3331-1249
Araujo, Angela M
Yan, Ka Yin Matthew
Botthof, Jan
Pérez-Gómez, Eduardo
Quintanilla, Miguel
Cuschieri, Kate
Caffarel, Maria M
Coleman, Nicholas
Over-expression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survival
Apollo - University of Cambridge Repository (staging)
2016
cervix
squamous cell carcinoma
oncostatin-M receptor
epithelial-mesenchymal transition
metastasis
STAT3
Apollo - University of Cambridge Repository (staging)
Apollo - University of Cambridge Repository (staging)
2016-06-23
2016-06-23
2016
en
Article
0007-0920
https://www.repository.cam.ac.uk/handle/1810/256462
1532-1827
Attribution-NonCommercial-ShareAlike 4.0 International
$\textit{Background }$ 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 over-expression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases migration and invasion $\textit{in vitro}$. We hypothesised that a major contribution to this phenotype would come from epithelial-mesenchymal transition (EMT). $\textit{Methods }$ We performed a comprehensive integrated study, involving $\textit{in vitro}$ cell line studies, $\textit{in vivo}$ animal models and numerous clinical samples from a variety of anatomical sites. $\textit{Results }$ 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 over-expressing cervical SCC cells produced consistent EMT changes and increased tumour sphere formation in suspension culture. In a mouse model, OSMR over-expressing 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 over-expression (N=251). $\textit{Conclusions }$ 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 over-expression in cervical SCCs.
This work was supported by Cancer Research UK (Programme Grant A13080).
This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group.
MRC
MR/R001146/1