June 10, 2003 Northwestern University researchers have found that a protein normally made in the body is critical for normal prostate growth regulation because mice that lack this protein develop an enlarged prostate. The excessive prostate growth in these animals resembles the human disease benign prostatic hyperplasia. In an article published in the June issue of Nature Medicine, lead authors Jennifer Doll and Veronica Stellmach, with their colleagues at the Feinberg School of Medicine at Northwestern University in Chicago and Umea University in Sweden, presented their studies of a protein called pigment epithelium-derived factor (PEDF).
The observation of too many cells in the prostate of the PEDF-null mice led the researchers to examine PEDF in human prostates and prostate cancers, as well as in cells cultured from these tissues.
PEDF was easily detected in healthy prostate tissue and normal prostate cells, but little to no PEDF was detected in most of the prostate cancer tissue samples examined or in isolated prostate cancer cells grown in the lab.
Androgens, the male sex hormones that regulate prostate growth, were shown to inhibit the production of PEDF. Because androgen ablation (removal) therapy is an important part of prostate cancer treatment, the researchers measured PEDF production following androgen ablation in prostate cancer cells. They found that PEDF production appeared to be turned back on in the cells of these tumors.
One important role recently defined for PEDF was its potent activity as an inhibitor of angiogenesis, the growth of new blood vessels, which is required for tumor growth. To determine if PEDF may be affecting cells in a tumor in addition to the cells lining the blood vessels, the researchers examined the effects of purified PEDF on cultured prostate cancer cells. They found that PEDF triggered an increased rate of prostate cancer cell death, and that this effect was enhanced if the cells were oxygen deprived, which occurs in growing tumors.
The anti-tumor action of PEDF was confirmed when treatment of prostate tumors in mice with PEDF resulted in tumor cell death.
Doll is a research associate and Stellmach a research assistant professor of pathology at the Feinberg School. Their co-researchers at the Feinberg School were Noel P. Bouck, emeritus professor of microbiology-immunology and a researcher at The Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Chung Lee, John T. Grayhack Professor of Urology Research and Cancer Center researcher; Lisa P. Abramson; Mona L. Cornwell; Michael R. Pins, associate professor of pathology; Jayme Borensztan-Brentan, Floyd Elroy Patterson Research Professor of Pathology; and Susan E. Crawford, associate professor of pathology and Cancer Center researcher. Anders R.J. Bergh, Umea University, Umea, Sweden, also contributed to these studies.
This research was supported in part by grants from the National Institutes of Health and the Department of Defense.
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