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Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB.血小板衍生生长因子（PDGF）在肿瘤发生中的作用：产生PDGF-BB的异种移植人黑色素瘤中血管结缔组织基质的发育
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Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-beta 1.在体外表现出血管生成的内皮细胞会对转化生长因子β1作出反应而增殖。
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血小板衍生生长因子BB（PDGF-BB）通过血小板衍生生长因子β受体在体外调节内皮细胞增殖和血管生成。

PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF beta-receptors.

作者信息

Battegay E J, Rupp J, Iruela-Arispe L, Sage E H, Pech M

机构信息

Department of Research and Internal Medicine, University Hospital Basel, Switzerland.

出版信息

J Cell Biol. 1994 May;125(4):917-28. doi: 10.1083/jcb.125.4.917.

DOI:10.1083/jcb.125.4.917
PMID:7514607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2120083/
Abstract

To delineate potential angiogenic roles of platelet-derived growth factor (PDGF), we have investigated PDGF and its receptors on bovine aortic endothelial cells that exhibit spontaneous angiogenesis in vitro (angiogenic endothelial cells). Initiation of cord/tube formation by angiogenic endothelial cells required bovine or human serum. Neutralization of PDGF-BB in human serum with a monoclonal anti-PDGF-BB antibody reduced cord/tube formation by 37 +/- 10%, whereas neutralizing anti-PDGF-AA and an IgG isotype-matched control antibody had no effect. DNA synthesis in response to PDGF-BB increased as the cords and tubes developed; furthermore, PDGF-BB induced the incorporation of BrdU in the nuclei of cells associated with these structures. PDGF beta-receptor (PDGF-beta) mRNA increased concomitantly with cord/tube formation, and PDGFR-beta were specifically localized by immunocytochemistry to developing and mature cords and tubes. However, PDGFR-beta transcripts and protein were undetectable in nonangiogenic endothelial cells, and PDGF alpha-receptor mRNA was not expressed in either endothelial cell strain. In contrast to nonangiogenic endothelial cells, angiogenic endothelial cells did not express the PDGF B-chain, the required ligand for the PDGFR-beta. We conclude that (a) PDGF-BB can contribute to angiogenesis in vitro, (b) PDGFR-beta are specific for cord/tube-forming endothelial cells and mediate endothelial proliferation and cord/tube formation, and (c) in angiogenic and nonangiogenic endothelial cells, the expression of PDGFR-beta and PDGF B-chain is inversely correlated. We therefore suggest that paracrine PDGF might amplify angiogenesis via direct action on endothelially expressed PDGFR-beta.

摘要

为了阐明血小板衍生生长因子（PDGF）潜在的血管生成作用，我们研究了PDGF及其受体在体外表现出自发性血管生成的牛主动脉内皮细胞（血管生成性内皮细胞）上的情况。血管生成性内皮细胞形成条索/管需要牛血清或人血清。用单克隆抗PDGF-BB抗体中和人血清中的PDGF-BB可使条索/管形成减少37±10%，而中和抗PDGF-AA及IgG同型对照抗体则无此作用。随着条索和管的形成，对PDGF-BB的DNA合成反应增加；此外，PDGF-BB诱导与这些结构相关的细胞细胞核中掺入BrdU。PDGFβ受体（PDGF-β）mRNA随着条索/管的形成而增加，并且通过免疫细胞化学将PDGFR-β特异性定位到发育中和成熟的条索及管上。然而，在非血管生成性内皮细胞中检测不到PDGFR-β转录本和蛋白，并且在两种内皮细胞系中均未表达PDGFα受体mRNA。与非血管生成性内皮细胞不同，血管生成性内皮细胞不表达PDGFR-β所需的配体PDGF B链。我们得出结论：（a）PDGF-BB可促进体外血管生成；（b）PDGFR-β对形成条索/管的内皮细胞具有特异性，并介导内皮细胞增殖和条索/管形成；（c）在血管生成性和非血管生成性内皮细胞中，PDGFR-β和PDGF B链的表达呈负相关。因此，我们认为旁分泌的PDGF可能通过直接作用于内皮细胞表达的PDGFR-β来放大血管生成。