HIGH expression of OSM and IL-6 are associated with decreased breast cancer survival: synergistic induction of IL-6 secretion by OSM and IL-1β


The cover for issue 21 of Oncotarget features Figure 7, "OSM and IL-1β promote IL-6 expression in a breast cancer cell-subtype specific manner," by Tawara, et al.

Using the Curtis TCGA dataset, the researchers have determined that there is a correlation between expression levels of OSM, IL-6, and IL-1 and reduced breast cancer patient survival.

Importantly, they confirm that OSM induces at least a 4-fold increase in IL-6 production from estrogen receptor-negative breast cancer cells in a manner that is dependent on STAT3 signaling.

Furthermore, OSM induces STAT3 phosphorylation and IL-1 promotes p65 phosphorylation to synergistically induce IL-6 secretion in ER MDA-MB-231 and to a lesser extent in ER+ MCF7 human breast cancer cells.

Figure 1: OSM and IL-6 are associated with decreased invasive breast cancer survival.

Dr. Cheryl Jorcyk from the Boise State University, Biomolecular Sciences Program & the Department of Biological Sciences, in Boise, ID, USA said, "Breast cancer-related morbidity and mortality remains one of the top concerns for women worldwide with 266,120 new cases of breast cancer predicted for 2018."

Despite new treatments and extensive preventative screening initiatives, breast cancer incidence remains flat, and there has been little improvement in the survival rate for stage IV metastatic breast cancer over the past decade.

Although the importance of IL-6 in cancer disease progression is well documented, anti-IL-6 therapies such as siltuximab have not produced clinically beneficial results for the treatment of solid tumors such as prostate, colorectal, lung, and ovarian cancers, although breast cancer was not yet tested.

Both IL-1 and IL-1 activate the same IL-1 receptor, while IL-1 is a membrane-bound protein and IL-1 is a soluble protein.

In this study, the authors investigate the effect of OSM, IL-6, and IL-1 on breast cancer patient survival as well as how these cytokines are interrelated in terms of cell signaling.

Using the Curtis TCGA data set, they found that high expression of OSM correlates with decreased breast cancer patient survival, similar to previous studies with IL-6.

They also demonstrate that co-treatment of ER breast cancer cells with both OSM and IL-1 leads to a synergistic increase in IL-6 secretion.

The Jorcyk Research Team concluded, "Collectively, our study demonstrates that OSM, IL-6, and IL-1β expression levels are correlated with each other and that cytokine signaling differs in an ER subtype-specific manner. OSM and IL-6 have previously been implicated in the production of proangiogenic factors such as VEGF to promote breast cancer progression and reduced patient survival [61]. Together, our results highlight the possible implications of multi-cytokine effects in the tumor microenvironment and have important clinical implications in that singular anti-cytokine therapies may not be sufficient for the successful treatment of metastatic breast cancer. In conclusion, this study substantiates the rationale for a therapeutic design that simultaneously targets multiple cytokines, such as OSM, IL-6, and IL-1β, as these cytokines are strongly correlated with each other in breast cancer."

Full text - https://doi.org/10.18632/oncotarget.26699

Correspondence to - Cheryl Jorcyk - [email protected]

Keywords - oncostatin M, interleukin-6 and oncostatin M, interleukin-1β, breast cancer, metastasis

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