Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.
Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.
Ferrara
N
N
Genentech, Inc., South San Francisco, California 94080.
Winer
J
J
Burton
T
T
Rowland
A
A
Siegel
M
M
Phillips
H S
HS
Terrell
T
T
Keller
G A
GA
Levinson
A D
AD
D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D006224:Cricetinae; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D006801:Humans; D017403:In Situ Hybridization; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors