Incorporation of endothelial progenitor cells into the neovasculature of malignant glioma xenograft.
Endothelial progenitor cells (EPCs) are important initiators of vasculogenesis in the process of tumor neovascularization. However, it is unclear how circulating EPCs contribute to the formation of tumor microvessels. In this study, we isolated CD34(+)/CD133(+) cells from human umbilical cord blood (HUCB) and obtained EPCs with the capacities of forming colonies, uptaking acetylated low-density lipoprotein (ac-LDL), binding lectins and expressing vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2, KDR), CD31 and von Willebrand factor (vWF). These EPCs were actively proliferative and migratory, and could formed capillary-like tubules in response to VEGF. When injected into mice bearing subcutaneously implanted human malignant glioma, EPCs specifically accumulated at the sites of tumors and differentiated into mature endothelial cells (ECs), which accounted for 18% ECs of the tumor microvessels. The incorporation of circulating EPCs into tumor vessel walls significantly affected the morphology and structure of the vasculature. Our results suggest that circulating EPCs constitute important components of tumor microvessel network and contribute to tumor microvascular architecture phenotype heterogeneity.
Zhang
Hua-rong
HR
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Chen
Fei-lan
FL
Xu
Chen-ping
CP
Ping
Yi-fang
YF
Wang
Qing-liang
QL
Liang
Zi-qing
ZQ
Wang
Ji Ming
JM
Bian
Xiu-wu
XW
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002448:Cell Adhesion; D002455:Cell Division; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D053262:Receptors, OX40 / Q000032:analysis; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous / Q000473:pathology*
D015703:Antigens, CD; D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D053262:Receptors, OX40