The Mechanisms of GM-CSF Inhibition of Breast Cancer Growth and Metastasis

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PROJECT SUMMARY (See Inslfucllons): The plan for the upcoming ROO phase of the award includes finalization of Specific Aim 2 using the clodronated liposomes as an alternate method for mononuclear phagocyte removal {as discussed In "Changes made to alms'), completion of Specific Aim 3 on the effects of GM-CSF on the growth, angiogenesis, and metastases in human breast cancer in Immunodeficient mice, and further investigation into monocyte and macrophage subpopulations generated in response to GM-CSF treatment. Thus the Specific Aims will address the following questions: Central Hypothesis (modification from original): GM-CSF treatment induces a phenotype switch In tumor infiltrating mononuclear phagocytes and triggers an anti-angiogenic program. Specific Aim 2 (fmm parent gmnt): To determine the cells responsible for sVEGFR-1 production In response to GM-CSF. Specific Aim 3 (from parent grant): Does GM-CSF Inhibit tumor growth, angiogenesis, and metastases of human tumors In nude mice? New Aims based on preliminary data generated from the parent grant and/or collaboration: Specific Aim 4: To determine if GM-CSF changes mononuclear phagocyte cell phenotypes using gene expression signatures and proteomic evaluation.