PDGFRbeta+-Perivascular Cells In Tumor Angiogenesis

描述(申请人提供)：血管由两种相互作用的细胞类型组成：内皮细胞和周细胞，内皮细胞构成血管管的内层，周细胞包裹血管管。虽然内皮细胞是两者中更好的特征，但周细胞现在正成为关注的焦点，因为它可能是肿瘤血管生成的重要调节因素。周细胞构成了一个不同种类的细胞群体，它们的个体发育和功能，特别是在肿瘤中，还不是很清楚。该项目将验证一种假设，即肿瘤相关的PDGFRbeta+血管周围细胞是具有分化为成熟周细胞的能力的前体细胞，并且它们是维持和生长肿瘤血管的关键血管细胞成分。具体目的1.鉴定和鉴定正常组织和恶性肿瘤组织中PDGFRbeta+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确定PDGFRbeta+血管周围细胞的特征。 具体目的2.研究PDGFRβ+血管周围细胞在肿瘤血管生成中的作用。我们将研究PDGFRbeta+细胞作为周细胞前体细胞和内皮细胞生存介质的潜在作用。具体目的3.揭示PDGFRbeta+血管周围细胞在肿瘤血管生成中的来源。我们将测试肿瘤相关的PDGFRbeta+血管周围细胞是来自骨髓，还是来自肿瘤所在的邻近正常组织。这项研究解决了肿瘤血管生成的一个新方面。它将检验与肿瘤相关的周细胞，即PDGFRbeta+血管周围细胞(PVC)是肿瘤血管的功能和工具组件的假设。这些结果将为开发PDGFRbeta+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，以期获得新的和稳定的血管形成，为治疗意义奠定重要基础。

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.