New link between testosterone and cancer cell aggression discovered

Researchers have found a number of genes that could help prostate cancer cells to grow and spread in response to testosterone.  This could explain some of the benefits of hormone therapy as well as offer a new way to potentially treat prostate cancer.

The researchers, based at the University of Newcastle, and funded by Prostate Cancer UK and the Movember Foundation, wanted to understand what effect the male sex hormone testosterone had on gene activity in prostate cancer cells. They hoped that by finding genes whose activity changed in response to the hormone, it could help suggest new ways to treat the disease.

They started by adding testosterone to cancer cells grown in the lab to see what happened to gene activity when hormone levels rose. At the same time, they used prostate cancer samples from men who’d had hormone therapy (which reduces testosterone levels) to see what effect lower hormone levels had on gene activity.

The scientists found that changing testosterone levels affected a group of genes linked to a process called glycosylation, where sugar groups are added to the surface of the cancer cells.  They noticed that lower testosterone levels in the samples from men on hormone therapy repressed the activity of a number of genes involved in the glycosylation process. However, when they added testosterone to cancer cells, the activity of these genes increased.

Additional benefit to hormone therapy

The scientists believe that the sugar groups (called glycans) added to the cell surface through glycosylation make the cancer cells more likely to survive and spread, making the cancer more aggressive. These results suggest that hormone therapy might benefit men by lowering the production of these glycans, thereby weakening the cancer cells.  However, by targeting the genes involved in glycosylation directly, it could offer a new approach to treating prostate cancer.

Although changes in glycosylation are fairly common in cancer, this finding helps us understand what is driving these changes in prostate cancer. This could open new doors to help diagnose more aggressive cancers earlier and identify which men might one day benefit from drugs developed to block the glycosylation process.

“Desperate need”

Dr Jennifer Munkley, who co-led the research project, said: “Our findings are very significant for future treatments as they identify a new group of molecules in prostate cancer, which could be targeted therapeutically.

“Now we have identified these glycans we will be able to develop strategies to inhibit them and help patients with this condition.

“Treatments targeting glycan sugar groups have been developed for other types of illness, such as breast cancer. Our results mean these treatments could also be used for prostate cancer.”

Simon Grieveson, Head of Research Funding at Prostate Cancer UK, said: “There’s a desperate need for more treatments for men with advanced prostate cancer, who currently have too few options available to them. However, in order to develop new, effective treatments, we need to understand more about the genetic make up of aggressive prostate cancers and identify what makes them tick. This promising research has unearthed a new group of genes which could play a part in cancer cell survival and development, and could pave the way for new treatments in the future.

“Although this work is still in its infancy and there is a long way to go before we could have a potential new treatment, we will be watching its progression with great interest.”