"Vasocrine" formation of tumor cell-lined vascular spaces: implications for rational design of antiangiogenic therapies.
Here we report that B16F10 murine melanoma cells mimic endothelial cell behavior and the angiogenic process in vitro and in vivo. Cord formation in vitro by tumor cells is stimulated by hypoxia and vascular endothelial growth factor (VEGF) and inhibited by antibodies against VEGF and the VEGF KDR receptor (VEGF receptor 2). We define regulation of tumor cell-derived vascular space formation by these vasoactive compounds as "vasocrine" stimulation. ICRF 159 (Razoxane; NSC 129943) prevents tumor cell but not endothelial cell cord formation in vitro, and the antiangiogenic drug TNP-470 (NSC 642492) inhibits endothelial but not tumor cell cord formation in vitro. Both drugs inhibit formation of blood-filled vascular spaces in vivo. These results bear on the anticipated action of ICRF 159 in human clinical trials and novel strategies for targeting tumor blood supplies.
Rybak
Susanna M
SM
Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Sanovich
Elena
E
Hollingshead
Melinda G
MG
Borgel
Suzanne D
SD
Newton
Dianne L
DL
Melillo
Giovanni
G
Kong
Dehe
D
Kaur
Gurmeet
G
Sausville
Edward A
EA
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D003510:Cyclohexanes; D015195:Drug Design; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011929:Razoxane / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011929:Razoxane; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077609:O-(Chloroacetylcarbamoyl)fumagillol