胶质瘤细胞FPR表达及其与肿瘤微血管构筑表型异质性的关系-病理学与病理生理学专业论文.docxVIP

第三军医大学博士学位论文 第三军医大学博士学位论文 3 3 The relationship between formylpeptide receptor expressed by human malignant glioma cells and tumor microvascular architecture phenotype heterogeneity Abstract Malignant gliomas are one of the highly vascularized tumors. Tumor neovascularization plays a crucial role for the growth and invasiveness of glioma, and is closely related with its malignant progress. The mechanism of angiogenesis and anti-angiogenesis has been one of the hotspots and focuses in cancer research, but therapeutical effect of anti-angiogenesis appears to be controversial. Tumor vascularity differs in many aspects from the vasculature of normal organs and tissues. Tumor microvascular architecture phenotype heterogeneity (T-MAPH), which was first proposed by our team, is considered as one of the important factors affecting the curative effect of anti-angiogenesis treatment strategy. In recent years, accumulating evidences indicate that adult endothelial progenitor cells (EPCs) had a close relationships with tumor vasculature, and had been considered as a promising target in anti-angiogenesis treatment strategy. tumors acquire their neovasculature by angiogenesis and vasculogenesis. These results proved that EPCs had participated in the development of T-MAPH, but the accurate function and mechanism of EPCs during the development of T-MAPH are unclear. Although it is unclear how EPCs contribute to the formation of tumor microvessels, emerging evidences suggest that chemotactic factors and its receptor play an important role in tumorigenesis, progression, metastasis, and neovascularization. Our previous studies have showed that formylpeptide receptor (FPR), a G-protein coupled receptor, was expressed by malignant glioma and related to the degree of maligancy and microvessel density within glioma tissue. Functional expression of FPR in glioma cells can promote the growth and neovascularization of tumor, and may be involved in the development of T-MAPH. It is importan