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

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. Oncotarget. 2019 Mar 12;10(21):2068-2085 Authors: Tawara K, Scott H, Emathinger J, Wolf C, LaJoie D, Hedeen D, Bond L, Montgomery P, Jorcyk C Abstract Chronic inflammation has been recognized as a risk factor for the development and maintenance of malignant disease. Cytokines such as interleukin-6 (IL-6), oncostatin M (OSM), and interleukin-1 beta (IL-1β) promote the development of both acute and chronic inflammation while promoting in vitro metrics of breast cancer metastasis. However, anti-IL-6 and anti-IL-1β therapeutics have not yielded significant results against solid tumors in clinical trials. Here we show that these three cytokines are interrelated in expression. Using the Curtis TCGA™ dataset, we have determined that there is a correlation between expression levels of OSM, IL-6, and IL-1β and reduced breast cancer patient survival (r = 0.6, p = 2.2 x 10-23). Importantly, we confirm that OSM induces at least a 4-fold increase in IL-6 production from estrogen receptor-negative (ER-) breast cancer cells in a manner that is dependent on STAT3 signaling. Furthermore, OSM induces STAT3 phosphorylation and IL-1β 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. Induction may be reduced...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research