title: Identification and significance of mobilized endothelial progenitor cells in tumor neovascularization of renal cell carcinoma.
abstract: Neovascularization is a key role of renal cell carcinoma (RCC) and the status of neovascularization in RCC is closely correlated with the tumor development and patient prognosis. Endothelial progenitor cells (EPCs) are considered as important building blocks for neovascularization. However, the role of mobilized EPCs in RCC remains unknown. In this study, the orthotopic RCC model was established to investigate the distribution, frequency, and significance of mobilized EPCs. We found that circulating endothelial progenitor cell (CEPC) levels and plasma angiogenic factors (vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) were higher in peripheral blood (PB) of the RCC than those in the normal group and positively correlated with each other. EPC levels in adjacent nonmalignant kidney tissue (AT) were significantly higher than those in tumor tissue (TT) and normal kidney tissue (NT), which were positively correlated with CEPC levels. VEGF, VEGF receptor-2 (Flk), and SDF-1 and its SDF-1 receptor (CXCR4) expression in AT was significantly higher than that in TT and NT. Levels of these angiogenic factors in AT were positively correlated with those in PB. Mean microvessel density (MVD) was higher in AT than in TT, and that in TT was slightly lower than that in NT. Our findings propose that mobilized EPCs play an important role in RCC neovascularization. EPCs in PB and AT can be used as a biomarker for predicting RCC progression.
authors.affiliation: Department of Urology and Center of Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Yu-Zheng
authors.initials: YZ
authors.lastname: Ge
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Wu
authors.forename: Ran
authors.initials: R
authors.lastname: Wu
authors.forename: Liu-Hua
authors.initials: LH
authors.lastname: Zhou
authors.forename: Rui-Peng
authors.initials: RP
authors.lastname: Jia
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2