INV OF ASTROCYTE CASPASE ACTV & CD40/CD40L SIGNALING INTERACTIONS IN ALZHEIMER?S

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Oncostatin M induces VEGF in human breast carcinoma cells: stimulation of angiogenesis in vitro and in vivo. Oncostatin M is a pleiotropic cytokine produced by many cell types, including neutrophils and tumor-associated mascrophages. OSM inhibits proliferation of breast cancer cells, and for this reason is being examined for its potential use in cancer treatment. Preliminary results from our lab show that OSM may promote pro-angiogenic factors in tumor cells. Additional studies show that OSM is expressed by tumor-associated neutrophils and breast cancer epithelial cells, but not by normal breast cancer tissue. Our data indicate that OSM stimulates breast cancer cells to produce angiogenesis-related matrix metalloproteinases (MMPs) and vascular endothelial growth factor-A (VEGF), which is an extremely potent angiogenic factor. Our goal is to understand the implications of VEGF induction to correctly evaluate the potential of OSM as a clinical cancer treatment. We hypothesize that VEGF produced by OSM-treated breast cancer cells will stimulate angiogenesis in vitro and in vivo. Our specific aims include: 1) To determine the OSM receptor and signaling pathway utilized to induce VEGF; 2) To demonstrate that VEGF produced by OSM-treated breast cancer cells will induce an angiogenic phenotype in cultured endothelial cells; and 3) To investigate the ability of OSM-induced VEGF to stimulate angiogenesis and promote the progression of breast carcinoma in vivo.