Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas

Jennifer A. Doll, Veronica M. Stellmach, Noël P. Bouck, Anders R.J. Bergh, Chung Lee, Lisa P. Abramson, Mona L. Cornwell, Michael R. Pins, Jayme Borensztajn, Susan E. Crawford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

252 Scopus citations

Abstract

Angiogenesis sustains tumor growth and metastasis, and recent studies indicate that the vascular endothelium regulates tissue mass. In the prostate, androgens drive angiogenic inducers to stimulate growth, whereas androgen withdrawal leads to decreased vascular endothelial growth factor, vascular regression and epithelial cell apoptosis. Here, we identify the angiogenesis inhibitor pigment epithelium-derived factor (PEDF) as a key inhibitor of stromal vasculature and epithelial tissue growth in mouse prostate and pancreas. In PEDF-deficient mice, stromal vessels were increased and associated with epithelial cell hyperplasia. Androgens inhibited prostatic PEDF expression in cultured cells. In vivo, androgen ablation increased PEDF in normal rat prostates and in human cancer biopsies. Exogenous PEDF induced tumor epithelial apoptosis in vitro and limited in vivo tumor xenograft growth, triggering endothelial apoptosis. Thus, PEDF regulates normal pancreas and prostate mass. Its androgen sensitivity makes PEDF a likely contributor to the anticancer effects of androgen ablation.

Original languageEnglish (US)
Pages (from-to)774-780
Number of pages7
JournalNature Medicine
Volume9
Issue number6
DOIs
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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