β1 integrins mediate tubule formation induced by supernatants derived from KSHV-infected cells

β1 integrins mediate tubule formation induced by supernatants derived from KSHV-infected cells
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DOI:
10.1159/000101995
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发表时间:
2007-01-01
期刊:
影响因子:
4.6
通讯作者:
Akula, Shaw M.
Akula, Shaw M.
中科院分区:
医学4区
文献类型:
--
作者:
Dyson, Ossie F.;Bryan, Benjaman A.;Akula, Shaw M.

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目的:血管生成被定义为新血管的形成。在最近完成的一项研究中,我们鉴定了源自原发性渗出性淋巴瘤 (PEL) 的卡波西肉瘤相关疱疹病毒 (KSHV) 感染细胞过度表达血管内皮生长因子 (VEGF),该因子具有介导基质胶上小管形成的倾向,这是血管生成的指标。本研究的目的是确定介导 KSHV 感染的 PEL 细胞上清液诱导的小管形成的受体分子。方法:通过在基质胶上进行的经典体外血管生成测定来确定在介导由 PEL 上清液驱动的小管形成中起作用的受体的身份。结果:针对 β1 整联蛋白的 RGD 肽、抗体和 siRNA 显着降低了 PEL 上清液诱导内皮细胞形成小管的能力。与来自未诱导或TPA诱导的PEL细胞的上清液一起孵育的内皮细胞中,β1整合素介导的小管形成达到相当的水平。有趣的是,β1 整合素似乎在细胞附着中没有起主要作用。结论:我们首次报告了 β1 整合素在 KSHV 感染的 PEL 细胞上清液支持的血管生成中的关键作用。版权所有 (C) 2007 S. Karger AG,巴塞尔。
Objective: Angiogenesis is defined as the formation of new blood vessels. In a recently concluded study, we identified Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells derived from primary effusion lymphoma ( PEL) to overexpress vascular endothelial growth factor (VEGF) that had the propensity to mediate tubule formation on a Matrigel, an indicator of angiogenesis. The objective of this study was to determine the receptor molecules that mediate the tubule formation induced by the supernatant derived from KSHV-infected PEL cells. Methods: The identity of receptor(s) that play a role in mediating tubule formation driven by PEL supernatant was determined by the classical in vitro angiogenesis assay conducted on a Matrigel. Results: RGD peptides, antibodies, and siRNA specific to beta 1 integrins significantly lowered the ability of the PEL supernatants to induce tubule formation by endothelial cells. beta 1 Integrins mediated tubule formation to comparable levels in endothelial cells that were incubated with supernatants derived from uninduced or TPA- induced PEL cells. Interestingly, the beta 1 integrins did not seem to have a major role in cellular attachment. Conclusion: We report for the first time a critical role for beta 1 integrins in angiogenesis supported by the supernatant from KSHV-infected PEL cells. Copyright (C) 2007 S. Karger AG, Basel.