Breast cancer cells co-cultured with neutrophils express endogenous oncostatin M (OSM)
2004
660 Oncostatin M (OSM) is a pleiotropic cytokine belonging to the interleukin-6 family and is expressed by several cell types, including activated human T-lymphocytes and macrophages. Recent evidence suggests that OSM may promote tumor progression by enhancing angiogenesis and metastasis. Tumor-associated and tumor-infiltrating neutrophils (TANs) and macrophages (TAMs) can 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. Our preliminary findings have shown that human neutrophils express OSM when co-cultured with human MDA-MB-231 breast cancer cells. Neutrophils were isolated from whole blood and then plated with breast cancer cells at different ratios. Neutrophils and breast cancer cells alone did not express OSM by immunohistochemistry, but when co-cultured together at a ratio of 10:1 for 3 to 5 days, neutrophils expressed OSM. In fibroblasts, OSM has also been shown to induce the expression of proteases, whose activities are reported to correlate with metastatic potential in tumor models. Matrix metalloproteinase (MMPs) and other proteolytic enzymes have been demonstrated to play critical roles in the angiogenesis cascade and to be markers of metastatic potential. Presently, we are examining whether neutrophil-derived OSM will induce proteases, such as MMPs, in co-cultured breast cancer cells utilizing ELISAs and immunoblotting. Positive findings could provide a rationale for the development of therapies that inhibit OSM. The potential to develop anti-OSM therapeutics is currently limitless: to date, there has been no attempt to inhibit OSM for the purposes of cancer therapy.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI