June 11, 2003
‘Lost’ Protein
Key To Prostate Treatment?
CHICAGO --- 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. |