Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF.
In contrast with the prevailing view that most tumors and metastases begin as avascular masses, evidence is presented here that a subset of tumors instead initially grows by coopting existing host vessels. This coopted host vasculature does not immediately undergo angiogenesis to support the tumor but instead regresses, leading to a secondarily avascular tumor and massive tumor cell loss. Ultimately, however, the remaining tumor is rescued by robust angiogenesis at the tumor margin. The expression patterns of the angiogenic antagonist angiopoietin-2 and of pro-angiogenic vascular endothelial growth factor (VEGF) suggest that these proteins may be critical regulators of this balance between vascular regression and growth.
Holash
J
J
Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Maisonpierre
P C
PC
Compton
D
D
Boland
P
P
Alexander
C R
CR
Zagzag
D
D
Yancopoulos
G D
GD
Wiegand
S J
SJ
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D017209:Apoptosis; D001808:Blood Vessels / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology; D005910:Glioma / Q000098:blood supply / Q000473:pathology; D017403:In Situ Hybridization; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; C467629:Angpt1 protein, rat; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008562:Membrane Glycoproteins; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors