Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, FL, USA.
Lab Invest. 2013 Jul;93(7):768-78. doi: 10.1038/labinvest.2013.71. Epub 2013 Jun 3.
Endothelial cell growth and proliferation are critical for angiogenesis; thus, greater insight into the regulation of pathological angiogenesis is greatly needed. Previous studies have reported on chemokine (C-X-C motif) ligand 1 (CXCL1) expression in epithelial cells and that secretion of CXCL1 from these epithelial cells induces angiogenesis. However, limited reports have demonstrated CXCL1 expression in endothelial cells. In this report, we present data that expand on the role of CXCL1 in human endothelial cells inducing angiogenesis. Specifically, CXCL1 is expressed and secreted from human endothelial cells. Interference of CXCL1 function using neutralizing antibodies resulted in a reduction in endothelial cell migration and viability/proliferation, the latter associated with a decrease in levels of cyclin D and cdk4. In vitro studies revealed that CXCL1 influenced neoangiogenesis through the regulation of epidermal growth factor and ERK1/2. In a xenograft angiogenesis model, interference of CXCL1 function resulted in inhibition of angiogenesis. A better understanding of the role of CXCL1 in the interactions between the endothelial and epithelial components will provide insight into how human tissues use CXCL1 to survive and thrive in a hostile environment.
内皮细胞的生长和增殖对于血管生成至关重要；因此，非常需要更深入地了解病理性血管生成的调节。先前的研究报告了趋化因子（C-X-C 基序）配体 1（CXCL1）在上皮细胞中的表达，并且这些上皮细胞分泌的 CXCL1 诱导血管生成。然而，有限的报道表明内皮细胞中存在 CXCL1 表达。在本报告中，我们提供的数据扩展了 CXCL1 在诱导人内皮细胞血管生成中的作用。具体来说，CXCL1 在人内皮细胞中表达和分泌。使用中和抗体干扰 CXCL1 的功能会导致内皮细胞迁移和活力/增殖减少，后者与细胞周期蛋白 D 和 CDK4 水平降低有关。体外研究表明，CXCL1 通过调节表皮生长因子和 ERK1/2 影响新血管生成。在异种移植物血管生成模型中，干扰 CXCL1 的功能会抑制血管生成。更好地了解 CXCL1 在内皮细胞和上皮细胞成分之间相互作用中的作用将深入了解人体组织如何利用 CXCL1 在恶劣环境中生存和茁壮成长。
