Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor.
Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and angiogenic growth factor that enhances endothelial cell invasion through the extracellular matrix (ECM). While various cell types express VEGF receptors, little is known about the biological actions of VEGF on nonendothelial cells. Therefore, the main objective of the present study was to determine the effect of VEGF on the in vitro invasiveness and proliferation of human MDA-MB-231 breast carcinoma cells and human HTR-8/SVneo trophoblast cells. Reverse-transcriptase polymerase chain reaction analysis demonstrated the presence of transcripts encoding VEGF receptors (VEGFR) -1, -2, and -3 as well as neuropilins-1 and -2 in the trophoblast cells, and the presence of transcripts encoding VEGFR-2 and neuropilins-1 and -2 in the breast carcinoma cells. Both cell lines also expressed transcripts for VEGF-A, -B, -C and -D, as well as for placenta growth factor (PlGF). Although incubation with exogenous VEGF-A(165) or VEGF-A(121) did not affect the rate of proliferation of either the trophoblast or the breast carcinoma cells, incubation with these molecules reduced their ability to invade through reconstituted ECM (Matrigel). The effect of VEGF-A(165) on the invasiveness of both cell lines was inhibited by the inclusion of a neutralizing antibody to VEGF. Exogenous VEGF-A(165) also decreased the cell surface expression of the urokinase-type plasminogen activator (a molecule required for invasion) by the breast carcinoma and trophoblast cells. These results indicate that the biological actions of VEGF on certain cell types may differ from the effects of this molecule on vascular endothelial cells, and therefore are relevant to angiogenesis-based therapies.
Fitzpatrick
Tania E
TE
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Lash
Gendie E
GE
Yanaihara
Atsushi
A
Charnock-Jones
D Stephen
DS
Macdonald-Goodfellow
Shannyn K
SK
Graham
Charles H
CH
D043925:Angiogenesis Inducing Agents / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology*; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D039942:Neuropilin-1 / Q000235:genetics; D039943:Neuropilin-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects; D055293:Receptors, Urokinase Plasminogen Activator; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D039943:Neuropilin-2; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C467484:VEGFA protein, human; C467485:VEGFB protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3