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Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas. Nat Med 2003 Jun;9(6):774-80

Date

05/13/2003

Pubmed ID

12740569

DOI

10.1038/nm870

Scopus ID

2-s2.0-0038240367 (requires institutional sign-in at Scopus site)   272 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.

Author List

Doll JA, Stellmach VM, Bouck NP, Bergh AR, Lee C, Abramson LP, Cornwell ML, Pins MR, Borensztajn J, Crawford SE

Author

Jennifer A. Doll PhD Assistant Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Androgens
Angiogenesis Inhibitors
Animals
Blood Vessels
Castration
Cobalt
Eye Proteins
Humans
Hyperplasia
Hypoxia
In Situ Nick-End Labeling
Male
Mice
Mice, Knockout
Mice, Nude
Neoplasm Transplantation
Neovascularization, Physiologic
Nerve Growth Factors
Pancreas
Prostate
Prostatic Neoplasms
Proteins
Rats
Serpins
Tumor Cells, Cultured