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

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Angiogenic factors; Angiogenic factors receptor; Endothelial progenitor cells; Renal cell carcinoma; Tumor-adjacent tissues.