Breast Cancer Cells Stimulate Neutrophils to Produce Ocostatin M: Potential Implications for Tumor Progression
Type of Culminating Activity
Master of Science in Biology
Julia Thom Oxford
Human neutrophils secrete, from their granules, a wide range of cytokines (IL-1α, TNF-α, and OSM) which have the capacity to direct the progress of an inflammatory reaction by influencing the activity of immune cells and tissues. Tumor-associated and tumor-infiltrating neutrophils (TANs) and macro phages (TAMs) account for as much as 50% of the total tumor mass in invasive breast carcinomas. It is thought that tumors secrete factors that elicit a wound-repair response from TAMs and TANs, and that this response inadvertently stimulates tumor progression. Oncostatin M (OSM) is a pleiotropic cytokine belonging to the interleukin-6 family and is expressed by several cell types including, activated human T-Iymphocytes, macrophages, and neutrophils. Recent evidence suggests that OSM may promote tumor progression by enhancing angiogenesis and metastasis. It has been shown that neutrophils can be stimulated to synthesize and rapidly release large quantities of the cytokine OSM. We show that human neutrophils secrete OSM when co-cultured with human breast cancer cells (MDA-MB-231 and T47D). Neutrophils isolated from whole blood or breast cancer cells alone express little OSM by immunohistochemistry and ELISA, but when co-cultured, neutrophils express and release high levels of OSM. We also show that breast cancer secreted granulocyte-macrophage colony- stimulating factor (GM-CSF) is important for the increase in neutrophil expressed OSM, and cell-to-cell contact is needed for the granular release of neutrophil-derived OSM. Importantly, neutrophil-derived OSM induces increased levels of vascular endothelial growth factor (VEGF) in co-culture and facilitates an increase in breast cancer cell detachment and invasive capacity. The role of neutrophils in inflammation and tumor progression suggests the possibility of anti-OSM cancer therapies effective against aggressive breast cancers such as inflammatory breast cancer, which has a poor diagnosis and survival rate.
Queen, Marisa M., "Breast Cancer Cells Stimulate Neutrophils to Produce Ocostatin M: Potential Implications for Tumor Progression" (2005). Boise State University Theses and Dissertations. 1457.