Effects of angiogenesis inhibitors on vascular network formation by human endothelial and melanoma cells.
Endothelial cells involved in vasculogenesis and angiogenesis are key targets in cancer therapy. Recent evidence suggests that tumor cells can express some genes typically expressed by endothelial cells and form extracellular matrix-rich tubular networks, phenomena known as vasculogenic mimicry. We examined the effects of three angiogenesis inhibitors (i.e., anginex, TNP-470, and endostatin) on vasculogenic mimicry in human melanoma MUM-2B and C8161 cells and compared them with their effects in human endothelial HMEC-1 and HUVEC cells. Anginex, TNP-470, and endostatin markedly inhibited vascular cord and tube formation by HMEC-1 and HUVEC cells in vitro, whereas tubular network formation by MUM-2B and C8161 cells was relatively unaffected. Endothelial cells expressed higher mRNA and protein levels for two putative endostatin receptors, alpha5 integrin and heparin sulfate proteoglycan 2, than melanoma cells, suggesting a mechanistic basis for the differential response of the two cell types to angiogenesis inhibitors. These findings may contribute to the development of new antivascular therapeutic agents that target both angiogenesis and tumor cell vasculogenic mimicry.
Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60614-3394, USA.
Daisy W J
DW
van der Schaft
Richard E B
RE
Seftor
Elisabeth A
EA
Seftor
Angela R
AR
Hess
Lynn M
LM
Gruman
Dawn A
DA
Kirschmann
Yumi
Y
Yokoyama
Arjan W
AW
Griffioen
Mary J C
MJ
Hendrix
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D003510:Cyclohexanes; D043169:Endostatins / Q000494:pharmacology; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000473:pathology*; D018716:Molecular Mimicry / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010455:Peptides; D011506:Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D043169:Endostatins; D010455:Peptides; D011506:Proteins; D012717:Sesquiterpenes; C111993:betapep-25 protein, synthetic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol