<p>OSM-induced CD44 contributes to breast cancer metastatic potential through cell detachment but not epithelial-mesenchymal transition</p>

Abstract

Background Hormone receptor status in human breast cancer cells is a strong indicator of the aggressiveness of a tumor. Triple negative breast cancers (TNBC) are aggressive, difficult to treat, and contribute to high incidences of metastasis by possessing characteristics such as increased tumor cell migration and a large presence of the transmembrane protein, cluster of differentiation 44 (CD44) on the cell membrane. Estrogen receptor-positive (ER+) cells are less aggressive and do not migrate until undergoing an epithelial-mesenchymal transition (EMT). Methods The relationship between EMT and CD44 during metastatic events is assessed by observing changes in EMT markers, tumor cell detachment, and migration following cytokine treatment on both parental and CD44 knockdown human breast tumor cells. Results ER+ T47D and MCF-7 human breast cancer cells treated with OSM demonstrate increased CD44 expression and CD44 cleavage. Conversely, ER- MDA-MB-231 human breast cancer cells do not show a change in CD44 expression nor undergo EMT in the presence of OSM. In ER+ cells, knockdown expression of CD44 by shRNA did not prevent EMT but did change metastatic processes such as cellular detachment and migration. OSM-induced migration was decreased in both ER+ and ER- cells with shCD44 cells compared to control cells, while the promotion of tumor cell detachment by OSM was decreased in ER+ MCF7-shCD44 cells, as compared to control cells. Interestingly, OSM-induced detachment in ER- MDA-MB-231-shCD44 cells that normally don’t detach at significant rates. Conclusion OSM promotes both EMT and tumor cell detachment in ER+ breast cancer cells. Yet, CD44 knockdown did not affect OSM-induced EMT in these cells, while independently decreasing OSM-induced cell detachment. These results suggest that regulation of CD44 by OSM is important for at least part of the metastatic cascade in ER+ breast cancer.

The Role of the IL-6 Cytokine Family in Epithelial–Mesenchymal Plasticity in Cancer Progression

“…Regarding the effects of OSM in mediating stemness and pluripotency, OSM was shown to induce a mesenchymal CD44 high/CD24 low phenotype in breast and pancreatic cancer cells, and this action was unique to OSM and not observed following IL-6 exposure in pancreatic cancer cells [ 48 , 95 , 99 ]. However, OSM-induced CD44 was shown to contribute to breast cancer metastatic potential through cell detachment but not EMP itself in another study [ 144 ]. Moreover, a recent report studied a collection of 28 cytokines and growth factors with altered mRNA expression in the TME of invasive human breast carcinomas and associated with relevant clinical parameters, such as tumour recurrence, metastasis or patient mortality.…”

Expression of pyroptosis-related genes are correlated with immune microenvironment and predict prognosis in ESCA

“…In this study, six genes used to establish risk model. Oncostatin M (OSM) can promote the potential of breast cancer metastasis (Covert et al 2019 ). Charged multivesicular body protein 7 (CHMP7) has been shown to be a risk gene for squamous cell carcinoma of the head and neck (Chen et al 2022 ).…”

The clinical relevance of OSM in inflammatory diseases: a comprehensive review

“…Paracrine and autocrine signaling of OSM has been shown in vivo to increase the amount of circulating tumor cells (CTC), epithelial to mesenchymal transition (EMT), as well as increased metastasis to lungs and decreased survival (109). OSM can also induce CD44 high / CD24 low phenotype allowing OSM to promote a CSC-like property, as well as increase detachment and migration of ER+ cells, while EMT remains independent of CD44 induction (112).…”