Effect of placenta growth factor-1 on proliferation and release of nitric oxide, cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor.
We investigated the effect of placenta growth factor-1 (P1GF-1) on cell growth and on the release of nitric oxide (NO), cyclic AMP (cAMP) and cyclic GMP (cGMP) in human malignant epithelial cells. A noteworthy increase in proliferation was induced in choriocarcinoma cells (BeWo) by P1GF-1 treatment, while breast cancer cells (CG-5) were minimally affected. Western blotting and immunocytochemistry demonstrated the expression of the P1GF-1 receptor fms-like tyrosine kinase-1 (Flt-1) in these models. NO was released in the BeWo culture medium as a result of P1GF-1 treatment, with maximal induction occurring after 6 h. Enhanced cAMP levels were observed after 80 min-6 h, while the amounts of cGMP produced were undetectable. In summary, PIGF-1 stimulates the proliferation of cell types that express Flt-1, other than endothelial cells. In BeWo cells, this effect is preceded by the induction of NO and cAMP as probable downstream effectors of Flt-1 activation.
Angelucci
C
C
Institute of Histology and Embryology, Catholic University of the Sacred Heart, Rome, Italy.
Lama
G
G
Iacopino
F
F
Maglione
D
D
Sica
G
G
D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology; D040281:Vascular Endothelial Growth Factor Receptor-1
D016326:Extracellular Matrix Proteins; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D009569:Nitric Oxide; D000242:Cyclic AMP; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D006152:Cyclic GMP