Increased angiogenic capabilities of endothelial cells from microvessels of malignant human gliomas.
Vascular endothelial cells (ECs) that initiate tumor angiogenesis may acquire distinct properties after conditioning in tumor microenvironment as compared to ECs in non-malignant tissues. Thus far, most in vitro studies of angiogenesis used ECs isolated from normal tissues, which may not fully represent the nature of ECs in tumor vasculature. In this study, glioma-derived microvascular ECs (GDMEC) were purified from human glioma tissues by incubating with magnetic beads coated with anti-CD105 antibody and highly pure (98%) preparations of GDMEC were obtained. These cells exhibited typical EC phenotype, and proliferated rapidly in culture. Interestingly, GDMEC expressed higher levels of VEGF receptors, flt-1 and flk-1, as compared to an established human EC cell line ECV304 and primary human umbilical vascular EC (HUVEC). Functionally, GDMEC were capable of forming intercellular junctions and tubule-like structures (TLS) of various sizes. Stimulation by VEGF further promoted TLS formation with diverse tubular walls by GDMEC. In contrast, TLS formed by ECV304 and HUVEC showed significantly different features. We further observed that Nordy, a synthetic lipoxygenase inhibitor, potently inhibited TLS formation by GDMEC. The results suggest that isolation of highly pure ECs derived from tumor tissues is more appropriate for studies of tumor angiogenesis and for test of potential anti-cancer therapeutic targets.
Bian
Xiu-wu
XW
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China. bianxiuwu@263.net
Jiang
Xue-feng
XF
Chen
Jian-hong
JH
Bai
Jia-si
JS
Dai
Chao
C
Wang
Qing-liang
QL
Lu
Jia-you
JY
Zhao
Wen
W
Xin
Rong
R
Liu
Ming-yu
MY
Shi
Jing-quan
JQ
Wang
Ji Ming
JM
D001254:Astrocytoma / Q000098:blood supply / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology; D005910:Glioma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D018189:Immunomagnetic Separation; D066298:In Vitro Techniques; D017705:Lignans; D009637:Masoprocol / Q000031:analogs & derivatives; D008833:Microcirculation / Q000473:pathology; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D017705:Lignans; D042461:Vascular Endothelial Growth Factor A; C510003:nordy; D009637:Masoprocol