Inhibition of tumor growth by the antiangiogenic placental hormone, proliferin-related protein.
Proliferin-related protein (PRP) is a potent placental antiangiogenic hormone. To test the antiangiogenic potential of PRP to block tumor growth, we engineered tumor cells to express this hormone. Both SV40-transformed BALB/c mouse 3T3 fibroblasts and rat C6 glioma cells have markedly reduced growth rates as tumors in mice if they express high levels of PRP. In both models, the small tumors that form are largely avascular, whereas control tumors are rich in blood vessels, consistent with PRP limiting tumor growth by preventing neovascularization of the tumors. The antiangiogenic effects of PRP are also detected on human endothelial cells, suggesting that the receptor and signaling pathway of this mouse hormone are conserved between mouse and human and may represent useful targets for the development of antiangiogenic therapeutics. That signaling pathway appears to involve an inhibition of arachidonic acid release, based on the ability of arachidonic acid to overcome the antiangiogenic effects of PRP.
Bengtson
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Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Linzer
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D016475:3T3 Cells; D020533:Angiogenesis Inhibitors / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D011257:Pregnancy Proteins / Q000235:genetics / Q000502:physiology*; D013539:Simian virus 40 / Q000235:genetics; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; C057074:Plfr protein, mouse; D011257:Pregnancy Proteins; C489178:Prl7d1 protein, rat