Abstract 4183: Differential expression of VEGF in breast cancer cells induced by gp130 cytokines

Glycoprotein 130 (gp130) is a glycosylated type 1 membrane protein and functions as a cytokine receptor modulating activity of the interleukin-6 (IL-6) family cytokines, which include IL-6, IL-11, IL-27, oncostatin M (OSM), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine (CLC), and neuropoietin (NP). This study was designed to determine differential expression of VEGF in breast cancer cells by IL-6 family cytokines, and to elucidate the molecular mechanisms and signaling pathways involved in cytokine-mediated VEGF induction. Triple negative breast cancer (TNBC) MDA-MB-231 and estrogen receptor positive/progesterone receptor positive/Her2 negative (ER+/PR+/Her2-) T47D cells were treated with three cytokines (25 ng/mL), OSM, IL-6, and LIF, and analyzed. Our results showed that all three cytokines increased levels of HIF1α by Western blot analysis. OSM lead to a greater production of VEGF compared to IL-6 and LIF, as measured by enzyme-linked immunosorbent assay (ELISA) and as seen by luciferase reporter assay. Of the three cytokines, OSM alone induced VEGF in TNBC MDA-MB-231 cells, and this effect was mediated by signal transducer activator of transcription 3 (STAT3) signaling. However, both OSM and IL-6 increased VEGF secretion levels in ER+/PR+/Her2- T47D breast cancer cells, and this signaling was mediated by both HIF1α and pSTAT3, utilizing ELISA and Western blot analysis. These results implicate OSM as the key gp130 cytokine inducing VEGF secretion, and also suggest that this induction is not always HIF1α dependent and is cell-line specific. Citation Format: Danielle S. Hedeen, Ken Tawara, Madhuri Nandakumar, Ryan Fox, David Chang, Alex Ide, Andrew Oler, Dollie LaJoie, Cheryl L. Jorcyk. Differential expression of VEGF in breast cancer cells induced by gp130 cytokines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4183. doi:10.1158/1538-7445.AM2015-4183