David Berman, an assistant professor of pathology, urology and oncology at The Johns Hopkins University School of Medicine, says that his team identified the unsuspected potential problem with the treatments that suppress testosterone, when they discovered that the gene that codes for the protein called nestin was active in lab-grown human prostate cancer cells.
With a view to determining 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, but found none.
However, the nestin gene was found to be active in prostate cancer cells isolated from patients who had died of metastatic prostate cancer, wherein cancer cells spread out from the prostate tumour.
Berman pointed out that it was almost certain that patients who eventually died because their disease metastasised were had received the androgen deprivation therapy, which reduces testosterone in the body is generally given when prostate cancers become aggressive and likely to metastasize.
He said that upon removal of androgen from the chemical mixture in which the cells live, the production of nestin increased.
With knowledge at hand that the nestin gene has long been suggested to play some role in cell growth and development, the researchers used laboratory sabotage called RNA interference to decrease the genetic expression of the gene.
They found that the cells were not able to move around and through other cells nearly as well as cells with normal nestin levels.
When prostate cancer cells with hampered nestin expression were transplanted into mice, the researchers found that such cells were less likely than normal prostate cancer cells to migrate to other parts of the body.
Berman, however, pointed out that though nestin expression seemed pivotal for metastasis in these experiments, it did not seem to make a difference in tumour 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," he said.