A popular prostate cancer treatment called androgen
deprivation therapy, which suppresses
testosterone, may encourage prostate cancer cells to
produce a protein that makes them more likely
to spread throughout the body, a new study by Johns
Hopkins researchers suggests.
Although the finding could eventually lead to changes
in this standard treatment for a
sometimes-deadly disease, the Johns Hopkins researchers
caution that their discovery is far too
preliminary for prostate cancer patients or physicians to
stop using it. The therapy is effective at
slowing tumor growth, they emphasized
David Berman, an assistant professor of
pathology,
urology and
oncology at the School of
Medicine, and his colleagues identified the unsuspected
potential problem after discovering that the
gene that codes for the protein, called nestin, was active
in lab-grown human prostate cancer cells.
Curious about whether prostate cancer cells in people
also produce nestin, the researchers
looked for it in cells taken from men who had surgery to
remove locally confined cancers of their
prostates, and found none. But when they looked for nestin
in prostate cancer cells isolated from
patients who had died of metastatic prostate cancer--in
which cancer cells spread out from the
prostate tumor--they found substantial evidence that the
nestin gene was active.
What was different, Berman speculated, is that
androgen deprivation therapy is generally given
only when prostate cancers become aggressive and likely to
metastasize. Because prostate cancer
growth is typically stimulated by testosterone, the
treatment is thought to slow tumor growth and
weaken the disease. Patients who eventually die because
their disease metastasizes are almost certain
to have received this type of therapy, he said.
Speculating that depriving cells of androgens might
also affect nestin expression, the
researchers experimented on a prostate cancer cell line
that depends on androgens to grow. When
they removed androgens from the chemical mixture that the
cells live in, the cells' production of
nestin increased.
Aware that the nestin gene has long been suggested to
play some role in cell growth and
development, Berman and his colleagues used a bit of
laboratory sabotage called RNA interference to
decrease the genetic expression of nestin and found that
these cells weren't able to move around and
through other cells nearly as well as cells with normal
nestin levels.
Prostate cancer cells with hampered nestin expression
were also less likely than normal prostate
cancer cells to migrate to other parts of the body when
transplanted into mice. However, while nestin
expression seemed pivotal for metastasis in these
experiments, it didn't seem to make a difference in
tumor growth.
"What all this suggests is that nestin levels
increased when prostate cancer cells are deprived
of androgens and may encourage the cells to metastasize,"
Berman said.
In addition to Berman, Johns Hopkins researchers
involved in this study were Wolfram
Kleeberger, G. Steven Bova, Matthew E. Nielsen, Mehsati
Herawi, Ai Ying Chuang and Jonathan I.
Epstein.
The research, published Oct. 1 in Cancer
Research, was funded by grants from the National
Institutes of Health, National Cancer Institute, Evensen
Family Foundation and German Cancer Aid
Foundation.
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