Contribution Of Inflammatory Cytokines To Cd44-Mediated Breast Cancer Metastatic Potential

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA The purpose of this study was to elucidate the relationship between the inflammatory cytokine oncostatin M (OSM) and cell migration-promoting CD44 in breast cancer metastasis. OSM-induced CD44 expression was studied in multiple human breast cancer cell lines, including triple negative (TNBC) MDA-MB-231 and estrogen receptor/progesterone receptor-positive (ER+/PR+) T47D and MCF-7 cells. Western blot analysis and RT-PCR demonstrated that OSM is capable of upregulating the expression of the standard form of CD44 (CD44s), as well as inducing multiple CD44 variants produced by alternative splicing. Confocal microscopy was performed and displayed highly organized CD44 around the edge of the cell after OSM treatment. OSM treatment also increased the breast cancer stem cell (BCSC) population (CD44+/CD24−), as measured by flow cytometry. To examine the importance of OSM-induced CD44 in tumor cell migration, we conducted migration assays with and without siCD44 and treatment with OSM. These results verified that OSM-induced CD44 is important for cellular migration. In conclusion, our studies demonstrate that OSM increases the expression of CD44s and its variants, as well as induce a BCSC phenotype. Furthermore, we show that OSM-induced CD44 plays a role in migration, which is an essential characteristic of breast cancer metastasis. Citation Format: Hunter Covert, Liliana Mellor. Contribution of inflammatory cytokines to CD44-mediated breast cancer metastatic potential. [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 5198. doi:10.1158/1538-7445.AM2015-5198