Androgen-Deprivation Therapy May Fuel Prostate Cancer

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Androgen-Deprivation Therapy May Fuel Prostate Cancer

Gandey

Medscape Medical News 2007. © 2007 Medscape

October 5, 2007 — A new study has found that androgen-deprivation therapy encourages prostate cancer cells to metastasize. It is a finding that may eventually lead to major changes in clinical practice, as experts look for alternatives to this popular treatment. But reporting in the October 1 issue of Cancer Research, investigators caution that their finding is far too preliminary to alter treatment and that androgen deprivation is effective in slowing tumor growth.

Prostate cancer growth is generally stimulated by testosterone, and treatment is thought to slow tumor growth and weaken disease. Most solid tumors, including prostate cancer, exhibit significant cell-to-cell heterogeneity with regard to tumor-forming and metastatic potential, write the researchers, led by Wolfram Kleeberger, MD, from the s Hopkins University School of Medicine, in Baltimore, land.

"Our data indicate that in a significant proportion of prostate cancers, nestin expression is required for colonizing distant sites in metastasis and thus may be a marker of metastasis-initiating cancer stem cells," they note.

In a news release promoting the findings, investigators say they did not expect to find a problem with the popular testosterone-suppressing treatments. The group reportedly looked for the issue only after discovering that the gene that codes for the protein nestin was active in lab-grown human prostate cancer cells.

As a result, the researchers questioned whether prostate cancer cells in people also produce nestin. Using cells taken from 254 men who had surgery to remove locally confined cancers of the prostate, investigators did not find any nestin. But when they looked for the protein in prostate cancer cells isolated from patients who had died of metastatic prostate cancer, they found evidence that the nestin gene was active.

Promoted Metastasis, but Didn't Seem to Affect Tumor Growth

Commenting in the news release, senior author Berman, MD, also from s Hopkins, said that androgen-deprivation therapy is generally given only when prostrate cancers become aggressive and are likely to metastasize. Patients who eventually die because their disease metastasizes are almost certain to have received this type of therapy, he said.

"What all this suggests," Dr. Berman said, "is that nestin levels increase when prostate cancer cells are deprived of androgens and may encourage the cells to metastasize."

The researchers also speculated that depriving cells of androgens might affect nestin expression. To explore this, they 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 production of nestin increased.

Nestin has long been said to play a role in cell growth and development. To explore this question, the researchers initiated ribonucleic acid interference to decrease the genetic expression of nestin. They found these cells were not able to move around and through other cells nearly as well as cells with normal nestin levels.

The investigators also found that prostate cancer cells with impaired nestin expression were less likely than normal prostate cancer cells to migrate to other parts of the body when transplanted in mice. But while nestin expression seemed pivotal for metastasis in these experiments, the researchers note, it did not seem to make a difference in tumor growth.

Cancer Res. 2007;67:9199-9206. Abstract

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