PDGFRbeta+-Perivascular Cells In Tumor Angiogenesis

描述（由申请人提供）：血管由两种相互作用的细胞类型组成：内皮细胞，形成血管的内衬;周细胞，包裹在血管周围。 虽然内皮细胞是更好的特点，这两个，周细胞现在成为焦点，作为潜在的重要调节肿瘤血管生成。 周细胞是一种异质的细胞群体，其个体发生和功能，特别是在肿瘤中的功能，还没有很好的理解。 该项目将检验肿瘤相关PDGFR β +血管周围细胞是祖细胞的假设，这些祖细胞具有分化为成熟周细胞的能力，并且它们是肿瘤血管维持和生长的关键血管细胞成分。具体目标1。 鉴定和表征正常和恶性组织中的PDGFR β +血管周围细胞。 我们将在三种肿瘤类型和相应的正常组织中表征PDGFR β +血管周围细胞。 具体目标2。 研究PDGFR β +血管周围细胞在肿瘤血管生成中的作用。 我们将研究PDGFR β +细胞作为周细胞祖细胞和作为内皮细胞存活介质的潜在作用。具体目标3。 揭示PDGFR β +血管周围细胞在肿瘤血管生成中的起源。 我们将检测肿瘤相关的PDGFR β +血管周围细胞是否来源于骨髓，或来源于肿瘤嵌入的邻近正常组织。这项研究提出了肿瘤血管生成的一个新方面。 它将检验肿瘤相关周细胞，PDGFR β +血管周细胞（PVC）是肿瘤血管的功能和工具成分的假设。 这些结果将为PDGFR β + PVC不仅作为肿瘤抗血管生成治疗的新靶点，而且作为组织中潜在的重要血管细胞成分，从而为治疗意义奠定重要基础，其中需要新的和稳定的血管形成。

DESCRIPTION (provided by applicant): Blood vessels consist of two interacting cell types: endothelial cells, which form the inner lining of the vascular tube, and pericytes, which wrap around the vascular tube. While endothelial cells are the better characterized of the two, pericytes are now coming into focus as potentially important regulators of tumor angiogenesis. Pericytes constitute a heterogeneous population of cells, and their ontogeny and function, specifically in tumors, is not well understood. This project will test the hypothesis that tumor-associated PDGFRbeta+ perivascular cells are progenitor cells that have the capacity to differentiate into mature pericytes and that they are a critical vascular cell constituent for the maintenance and growth of tumor vessels. Specific Aim 1. Identify and characterize PDGFRbeta+ perivascular cells in normal and malignant tissues. We will characterize PDGFRbeta+ perivascular cells in three tumor types and in the respective normal tissues. Specific Aim 2. Study function of PDGFRbeta+ perivascular cells in tumor angiogenesis. We will examine the potential role of PDGFRbeta+ cells as pericyte progenitor cells and as survival mediators for endothelial cells. Specific Aim 3. Reveal the origin of PDGFRbeta+ perivascular cells in tumor angiogenesis. We will test whether tumor-associated PDGFRbeta+ perivascular cells originate from the bone marrow, or from adjacent normal tissue in which the tumor is embedded. The research addresses a novel aspect in tumor angiogenesis. It will test the hypothesis that the tumor-associated pericyte, the PDGFRbeta+ perivascular cell (PVC), is a functional and instrumental component of tumor vessels. The results will set an important foundation for therapeutic implications by exploiting PDGFRbeta+ PVC not only as novel targets for anti-angiogenic therapies in tumors but also as potentially important vascular cell constituents in tissues in which new and stable blood vessel formation is desired.