Placental growth factor is a survival factor for tumor endothelial cells and macrophages.
The vascular endothelial growth factor (VEGF)-related factor, placental growth factor (PlGF),has been shown recently to play an important role in pathological VEGF-driven angiogenesis. In this study, we examine the effects of mPlGF/PlGF-2 overexpression in tumors grown from glioma cells containing a tetracycline-regulated mPlGF cDNA. Overexpression of mPlGF leads to increased tumor growth and vascular survival. When tetracycline is used to abruptly withdraw mPlGF overexpression, we see increased apoptosis in both vascular cells and macrophages. In addition, PlGF-2 induces survival gene expression and inhibits apoptosis in vitro. Thus, we propose that PlGF-2 contributes to tumor angiogenesis by providing increased survival function to endothelial cells and macrophages.
Adini
Avner
A
Division of Cancer and Angiogenesis, Department of Pathology, The Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Kornaga
Tad
T
Firoozbakht
Farshid
F
Benjamin
Laura E
LE
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D005910:Glioma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D000077022:Survivin; D015854:Up-Regulation
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D000077022:Survivin; D000072483:Placenta Growth Factor