When some of the most common cancers spread in the body, they often head for the bones. Once there, they typically eat away the good, strong tissue, leaving a soft and crumbly structure in their wake. It is a painful and debilitating condition. But prostate cancer is different. Unlike any other cancer, when prostate cancer spreads to the bones – as it does in 80 percent of advanced cases – it actually stimulates new bone to grow.
For a long time scientists have not known how to study this form of cancer. They have managed to develop useful animal models for many cancers to help study the cause and treatment of the disease, but it has been difficult to come up with one to study prostate cancer. Dr. Tom Rosol, a veterinarian in The Ohio State University’s Comprehensive Cancer Center, explains that the problem has been that every time human prostate cancer cells are put into animals, the cells stop behaving like they do in humans.
Rosol, who has spent 19 years tracking the molecular intricacies of cancer metastasis, needed to find an animal model that worked. He hypothesised that maybe healthy prostate tissue – as well as cancerous tissue – was capable of sending growth signals to bone. There are only two animals that get prostate cancer – dogs and man. The canine prostate gland and its diseases are very similar to that observed in man, and canine prostate tissue produces many of the same bioactive factors believed to be important in metastatic disease.
Since obtaining healthy human tissue would be difficult, Rosol decided to experiment with small bits of healthy prostate tissue from dogs. He inserted small pieces of the prostate tissue underneath the skin of adult nude mice, right at the skullcap, or calvaria, and waited to see what happened.
Rosol and his team were shocked by the results. Within two weeks, the density of the calvaria had almost doubled. This finding was really exciting, not just because of the speed of the reaction, but because there are very few things in nature that induce bone growth.
It is not entirely clear what causes the bone to form, but it is probably a complex mixture of growth factors such as parathyroid hormone-like protein and endothelin-1, among others, acting in concert with receptive agents in the hosts’ bone. Rosol believes that endothelin-1 plays a critical role, however. His research team is already working with a drug designed to block endothelin-1 activity and it looks like it may be working.
Rosol says it is important to continue to develop new and workable animal models to better understand cancer. Because of earlier detection and new treatments, cancer patients are living longer than ever, and in many advanced cases, they have to deal with cancer in their bones. Rosol and his team hope that discovery of the mechanisms of bone formation at sites of prostate cancer metastasis in bone will eventually lead to the successful prevention of this terrible manifestation of prostate cancer.
Rosol adds, ironically, that a terrible process like metastasis may hold the very clues to an effective treatment for other diseases, like osteoporosis, that involve bone destruction.
The study is published in a recent issue of The Prostate.
Science Daily News
13 June 2002
