Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma

Abstract

Cervical carcinoma is the second most common cause of cancer deaths in women worldwide. Treatments have not changed for decades and survival rates for advanced disease remain low. An exciting new molecular target for the treatment of cervical squamous cell carcinoma (SCC), and possibly for SCCs at other anatomical sites, is the oncostatin M receptor (OSMR). This cell surface cytokine receptor is commonly copy number gained and overexpressed in advanced cervical SCC, changes that are associated with significantly worse clinical outcomes. OSMR overexpression in cervical SCC cells results in enhanced responsiveness to the major ligand oncostatin M (OSM), which induces several pro-malignant effects, including a pro-angiogenic phenotype and increased cell migration and invasiveness. OSMR is a strong candidate for antibody-mediated inhibition, a strategy that has had a major impact on haematological malignancies and various solid tumours such as HER2-positive breast cancers. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

“…Recent studies indicate that OSM-R is overexpressed in advanced cervical squamous cell carcinomas making the cells susceptible for OSM signals. However, high expression of OSM-R in cervical cancers is associated with worse clinical outcome and OSM signals were described to initiate several pro-tumorigenic effects (37,38). For this reason, OSM-R is recommended as a candidate for antibody-mediated inhibition to block pro-malignant effects (38,39).…”

STAT3-mediated SMAD3 activation underlies Oncostatin M-induced Senescence

“…1,[19][20][21][22][23][24]28,33,74,[87][88][89][90][91][92][93] For example, in addition to the increased OSM levels in the breast TME, breast cancer cells also display elevated OSMR expression levels, which is associated with adverse clinical outcomes. 32,71,83,88,92,94 Notably, the more aggressive basal-like or triple-negative breast cancer subtype expresses markedly higher levels of OSMR when compare with the less aggressive luminal subtype. 71 Moreover, elevated OSMR expression correlates with increased expression of the cancer stem cell (CSC) marker CD44.…”

Oncostatin M and interleukin-31: Cytokines, receptors, signal transduction and physiology

“…In cervical squamous cell carcinoma (SCC) a frequent gain in copy number of the OSMR gene is observed, which results in overexpression at the cell surface and enhanced responsiveness to OSM. These changes were associated with significantly worse clinical outcomes which made the OSMRb an interesting therapeutic target in this cancer entity (reviewed in [49]). Similarly, in breast cancer high OSMR expression correlated with shorter recurrence-free and overall survival [50].…”

“…Within the last three years excellent reviews have been published which in detail summarize findings on in vitro and in vivo OSM biology in general [91] or with a focus on specified tissues, cancers or metabolic processes [49,[92][93][94][95][96]. Therefore, in this review only recent findings in genetically modified mouse models targeting either OSM itself or the OSMRb will be summarized.…”