Wachstumsfaktor-vermittelte Rekrutierung von Entzündungszellen ins Tumor-Stroma: Funktionelle Rolle in Angiogenese und Tumorprogression

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In malignant tumors of the HaCaT skin SCC model persistent angiogenesis, the prerequisite for tumor invasion, is preceded by the induction of a strong and persistent inflammation. In our 1rst year of funding we demonstrated a crucial contribution of Gr1+/CD11b+ cells to angiogenesis and tumor invasion in skinSCCs. Additionally, we identified IL-6 and SDF-1 as well as MMP-9 and MMP-13 as important contributors to the establishment of an angiogenesis and invasion promoting inflammatory infiltrate. Based on these data we will continue to analyze the function of the inflammatory infiltrate in tumor angiogenesis and invasion. We will characterize the phenotype of the angiogenesis promoting Gr1+/CD11b+ cells specifically with respect to an MDSC phenotype. Furthermore we will determine the differentiation status of macrophages (M1 versus TAM/M2) in the context of their interaction with tumor associated Gr1+/CD11b+ cells. Differential macrophage functions in the induction and maintenance of angiogenesis will be identified. The effect of specific growth factors such as IL-1β, IL-6 and SDF-1 on the recruitment and differentiation of tumor associated macrophages and Gr1+ cells will be analyzed and their influence on promoting tumor angogenesis will be characterized. Ultimately we aim at blocking those factor-mediated interactions that are essential for the recruitment and differentiation of an angiogenesis and invasion promoting inflammatory infiltrate.