Nature Medicine
9, 774 - 780 (2003)
Published online: 12 May 2003; | doi:10.1038/nm870
Pigment epithelium−derived factor regulates the vasculature and mass of the prostate and pancreasJennifer A Doll1, 7, Veronica M Stellmach1, 7, Noël P Bouck2, 3, Anders RJ Bergh6, Chung Lee4, Lisa P Abramson5, Mona L Cornwell1, Michael R Pins1, Jayme Borensztajn1
& Susan E Crawford1, 31
Department of Pathology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, Illinois, 60611, USA. 2
Department of Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, Illinois, 60611, USA. 3
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, Illinois, 60611, USA. 4
Department of Urology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, Illinois, 60611, USA. 5
Children's Memorial Hospital, Division of Surgery, 2300 Childrens Plaza, Chicago, Illinois, 60614, USA. 6
Department of Biomedical Sciences, Pathology, 6M Building, Umeå University, 90187, Umeå, Sweden. 7
These authors contributed equally to this work.
Correspondence should be addressed to Susan E Crawford scrawford@northwestern.eduAngiogenesis 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.
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