Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University, 210006 Nanjing, China.
Biomed Pharmacother. 2013 Sep;67(7):643-9. doi: 10.1016/j.biopha.2013.06.009. Epub 2013 Jul 5.
The aim of this study was to detect the levels of CD34(+)/Flk-1(+) endothelial progenitor cells (EPCs) in renal cell carcinoma (RCC)-adjacent tissues and explore the correlation of RCC-adjacent tissues EPCs and tumor invasion.
An orthotopic renal tumor model was successfully established. At days 7, 12, 17 and 21, eight mice were put to death respectively. Tumor diameters were measured and RCC-adjacent tissues were collected. The percentage of EPCs within the kidney mononuclear cell population was detected. The expression levels of Stromal cell-derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF) and their receptors CXCR4, Flk-1 mRNA and protein were probed respectively. And then, mean microvascular density (MVD) was examined.
EPC numbers in RCC-adjacent tissues were significantly higher than those in control groups. The ratios of EPCs were increased gradually, and so were tumor diameters. The levels of SDF-1 and VEGF were also increased gradually, but significantly reduced compared with control group at each time point. In addition, CXCR4 and Flk-1 expression were decreased gradually.
Our investigation suggested that EPCs in RCC-adjacent tissues play an important role in early stage RCC invasion, involving the promotion on angiogenesis through releasing several angiogenic factors.
本研究旨在检测肾细胞癌（RCC）旁组织中 CD34(+)/Flk-1(+)内皮祖细胞（EPCs）的水平，并探讨 RCC 旁组织 EPCs 与肿瘤侵袭的相关性。
成功建立了原位肾肿瘤模型。在第 7、12、17 和 21 天，分别处死 8 只小鼠。测量肿瘤直径并收集 RCC 旁组织。检测肾单核细胞群体中 EPCs 的百分比。分别检测基质细胞衍生因子-1（SDF-1）、血管内皮生长因子（VEGF）及其受体 CXCR4、Flk-1 mRNA 和蛋白的表达水平。然后，检查平均微血管密度（MVD）。
RCC 旁组织中的 EPC 数量明显高于对照组。EPCs 的比例逐渐增加，肿瘤直径也随之增加。SDF-1 和 VEGF 的水平也逐渐增加，但在每个时间点与对照组相比均显著降低。此外，CXCR4 和 Flk-1 的表达逐渐降低。
我们的研究表明，RCC 旁组织中的 EPCs 在早期 RCC 侵袭中发挥重要作用，通过释放多种血管生成因子促进血管生成。
