Scatter factor induces blood vessel formation in vivo.
Scatter factor (also known as hepatocyte growth factor) is a glycoprotein secreted by stromal cells that stimulates cell motility and proliferation. In vitro, scatter factor stimulates vascular endothelial cell migration, proliferation, and organization into capillary-like tubes. Using two different in vivo assays, we showed that physiologic quantities of purified native mouse scatter factor and recombinant human hepatocyte growth factor induce angiogenesis (the formation of new blood vessels). The angiogenic activity was blocked by specific anti-scatter factor antibodies. Scatter factor induced cultured microvascular endothelial cells to accumulate and secrete significantly increased quantities of urokinase, an enzyme associated with development of an invasive endothelial phenotype during angiogenesis. We further showed that immunoreactive scatter factor is present surrounding sites of blood vessel formation in psoriatic skin. These findings suggest that scatter factor may act as a paracrine mediator in pathologic angiogenesis associated with human inflammatory disease.
Grant
D S
DS
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Kleinman
H K
HK
Goldberg
I D
ID
Bhargava
M M
MM
Nickoloff
B J
BJ
Kinsella
J L
JL
Polverini
P
P
Rosen
E M
EM
D000818:Animals; D002417:Cattle; D003094:Collagen; D003315:Cornea / Q000098:blood supply; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D007797:Laminin; D051379:Mice; D009389:Neovascularization, Pathologic; D010960:Plasminogen Activators / Q000378:metabolism; D011509:Proteoglycans; D011565:Psoriasis / Q000378:metabolism; D051381:Rats
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D017228:Hepatocyte Growth Factor; D003094:Collagen; D010960:Plasminogen Activators