Dyson Ossie F, Bryan Benjaman A, Lambert Phelps J, Ford Patrick W, Akula Shaw M
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Intervirology. 2007;50(4):245-53. doi: 10.1159/000101995. Epub 2007 Apr 25.
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.
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.
RGD peptides, antibodies, and siRNA specific to beta1 integrins significantly lowered the ability of the PEL supernatants to induce tubule formation by endothelial cells. beta1 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 beta1 integrins did not seem to have a major role in cellular attachment.
We report for the first time a critical role for beta1 integrins in angiogenesis supported by the supernatant from KSHV-infected PEL cells.
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,我们发现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),该因子有在基质胶上介导小管形成的倾向,而基质胶上的小管形成是血管生成的一个指标。本研究的目的是确定介导由KSHV感染的PEL细胞上清液诱导的小管形成的受体分子。
通过在基质胶上进行的经典体外血管生成试验来确定在介导由PEL上清液驱动的小管形成中起作用的受体的身份。
针对β1整合素的RGD肽、抗体和siRNA显著降低了PEL上清液诱导内皮细胞小管形成的能力。β1整合素在与未诱导或TPA诱导的PEL细胞上清液孵育的内皮细胞中介导小管形成至相当水平。有趣的是,β1整合素似乎在细胞附着中没有主要作用。
我们首次报道了β1整合素在由KSHV感染的PEL细胞上清液支持的血管生成中的关键作用。