Prostate cancer treatment may encourage spread of cancer cells

Oct 3 2007

According to a new study by researchers in the U.S. the popular prostate cancer treatment, androgen deprivation therapy, may in fact encourage the spread of cancer cells throughout the body.

It is common for men with advanced prostate cancer to be given therapy which blocks their body’s production or use of testosterone; this is because the hormone encourages the growth of prostate cancer.

The treatment 'androgen deprivation therapy' (ADT), is not considered to be a cure but is thought to delay the growth and spread of tumors which are inoperable.

However this new research suggests that the therapy encourages the production of a protein that makes the cancer cells more likely to proliferate.

The team at the Johns Hopkins School of Medicine do however say that their discovery is very much a preliminary one and they do not advise androgen deprivation therapy should cease as the therapy as it is effective at slowing down the growth of tumors.

The finding could however ultimately lead to changes in standard treatment for what can be a deadly disease.

The researchers identified the unsuspected potential problem with ADT following the discovery that the gene that codes for the protein Nestin was active in lab-grown human prostate cancer cells.

David Berman, an assistant professor of pathology, urology and oncology at Johns Hopkins and his colleagues became interested in whether prostate cancer cells in people also produce Nestin.

The team searched for Nestin in cells taken from men who had surgery to remove locally confined cancers of their prostates but found none.

However when they looked for Nestin in prostate cancer cells isolated from patients who had died of metastatic prostate cancer, where the cancer cells had spread out from the prostate tumor, they found substantial evidence that the Nestin gene was active.

Berman suggests that the difference was that androgen deprivation therapy is a treatment generally given only when prostate cancers become aggressive and likely to metastasize because the treatment is thought to slow tumor growth and weaken the disease.

Berman says patients who eventually die because their disease metastasizes are almost certain to have received this type of therapy.

The suspicion that by depriving cells of androgens might also affect Nestin expression, led the researchers to experiment on a prostate cancer cell line that depends on androgens to grow.

They found that when they removed androgens from the chemical mixture the cells live in, their production of Nestin increased.

By using the knowledge that the Nestin gene played some role in cell growth and development, Berman and his colleagues then used RNA interference to decrease the genetic expression of Nestin and found that these cells were not able to move around and through other cells nearly as well as cells with normal Nestin levels.

Tumor cells from patients never put on ADT did not produce Nestin and even patients whose cancer had already spread showed no Nestin production in the tumor cells if they had never been treated with ADT.

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.

The researchers say even though Nestin seemed pivotal for metastasis in these experiments, it did not seem to affect tumor growth.

Berman says the suggestion is that Nestin levels increased when prostate cancer cells are deprived of androgens and may encourage the cells to metastasize.

The research says Berman found that Nestin is produced by prostate cancer cells in response to androgen deprivation and appears to arise in patients who take ADT longer than 6 months.

The research is published in the October 1st issue of Cancer Research and was funded by grants from the National Institutes of Health, National Cancer Institute, Evensen Family Foundation, and German Cancer Aid Foundation.