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

生长因子介导的炎症细胞募集到肿瘤基质中：在血管生成和肿瘤进展中的功能作用

• 批准号: 38806198
• 负责人: Professorin Dr. Margareta M. Müller
• 金额: --
• 依托单位: Fakultät Medical and Life Sciences
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/38806198?language=en
• 关键词: Wachstumsfaktor; vermittelte; Rekrutierung; von; Entz

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.

在HaCaT皮肤SCC模型的恶性肿瘤中，持续的血管生成是肿瘤侵袭的先决条件，在此之前会诱导强烈而持续的炎症。在我们资助的第一年，我们证明了Gr1+/CD11b+细胞对皮肤sccs血管生成和肿瘤侵袭的重要贡献。此外，我们发现IL-6和SDF-1以及MMP-9和MMP-13是建立血管生成和促进炎症浸润的重要贡献者。基于这些数据，我们将继续分析炎症浸润在肿瘤血管生成和侵袭中的作用。我们将描述血管生成促进Gr1+/CD11b+细胞的表型，特别是相对于MDSC表型。此外，我们将在巨噬细胞与肿瘤相关的Gr1+/CD11b+细胞相互作用的背景下确定巨噬细胞（M1与TAM/M2）的分化状态。巨噬细胞在诱导和维持血管生成中的不同功能将被确定。分析IL-1β、IL-6、SDF-1等特异性生长因子对肿瘤相关巨噬细胞和Gr1+细胞募集和分化的影响，并探讨其促进肿瘤血管生成的作用。最终，我们的目标是阻断这些因子介导的相互作用，这些相互作用对于血管生成和入侵促进炎症浸润的募集和分化至关重要。