Platelet-derived growth factor-b enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment
Platelet-derived growth factor-b enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment
复制标题
DOI：
10.1016/s0002-9440(10)63905-3
复制
发表时间：
2003-04-01
影响因子：
6
通讯作者：
Cheng, SY
中科院分区：
文献类型：
--
作者：
Guo, P;Hu, B;Cheng, SY
血小板衍生生长因子（PDGF）-B及其受体（PDGF-R）β在人胶质瘤中过表达，并负责将内皮细胞周围细胞募集到血管中。为了确定PDGF-B在胶质瘤血管生成中的作用，我们在U87 MG胶质瘤细胞中过表达PDGF-B。尽管PDGF-B刺激U87 MG细胞中PDGF-R β的酪氨酸磷酸化，但用重组PDGF-B或在U87 MG细胞中过表达PDGF-B对其增殖没有影响。然而，在U87 MG/PDGF-B细胞的条件培养基中分泌的PDGF-B的增加促进表达PDGF-R β的内皮细胞的迁移，而来自U87 MG细胞的条件培养基不增加细胞迁移。在小鼠中，PDGF-B在U87 MG细胞中的过表达通过刺激新生血管中血管内皮生长因子（VEGF）的表达和吸引血管相关周细胞来增强颅内胶质瘤的形成。当PDGF-B和VEGF在U87 MG肿瘤中同时过表达时，毛细血管相关周细胞显著增加，如在U87 MG/VEGF（165）/ PDGF-B胶质瘤中所见。由于周细胞的募集，VEGF诱导的肿瘤附近的血管迁移到这些肿瘤的中心区域。这些数据表明，PDGF-B是一个旁分泌因子在U87 MG胶质瘤，PDGF-B增强胶质瘤血管生成，至少部分，通过刺激VEGF表达在肿瘤内皮细胞和周细胞募集新生血管。
Platelet-derived growth factor (PDGF)-B and its receptor (PDGF-R) beta are overexpressed in human gliomas and responsible for recruiting peri-endothelial cells to vessels. To establish the role of PDGF-B in glioma angiogenesis, we overexpressed PDGF-B in U87MG glioma cells. Although PDGF-B stimulated tyrosine phosphorylation of PDGF-Rbeta in U87MG cells, treatment with recombinant PDGF-B or overexpression of PDGF-B in U87MG cells had no effect on their proliferation. However, an increase of secreted PDGF-B in conditioned media of U87MG/PDGF-B cells promoted migration of endothelial cells expressing PDGF-Rbeta, whereas conditioned media from U87MG cells did not increase the cell migration. In mice, overexpression of PDGF-B in U87MG cells enhanced intracranial glioma formation by stimulating vascular endothelial growth factor (VEGF) expression in neovessels and by attracting vessel-associated pericytes. When PDGF-B and VEGF were overexpressed simultaneously by U87MG tumors, there was a marked increase of capillary-associated pericytes as seen in U87MG/VEGF(165)/ PDGF-B gliomas. As a result of pericyte recruitment, vessels induced by VEGF in tumor vicinity migrated into the central regions of these tumors. These data suggest that PDGF-B is a paracrine factor in U87MG gliomas, and that PDGF-B enhances glioma angiogenesis, at least in part, by stimulating VEGF expression in tumor endothelia and by recruiting pericytes to neovessels.