Renal cell carcinoma-adjacent tissues enhance mobilization and recruitment of endothelial progenitor cells to promote the invasion of the neoplasm

Abstract

AimsThe 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. MethodsAn 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. ResultsEPC 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. ConclusionsOur 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.