Dogs key to understanding prostate cancer

June 12, 2002

COLUMBUS, Ohio - Science is going to the dogs - literally - to clear up some of the mystery surrounding prostate cancer and how it spreads.

When some of the most common cancers spread, 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 all advanced cases - it actually stimulates new bone to grow, not erodes it.

"We've really been stumped on how to study this," says Dr. Tom Rosol, a veterinarian in The Ohio State University's Comprehensive Cancer Center. Scientists have managed to develop useful animal models for many cancers to help study the cause and treatment of the disease, but it's been difficult to come up with one to study prostate cancer. "That's because every time we put human prostate cancer cells in animals, they stop acting like they do in humans," says Rosol.

Rosol, who has spent 19 years tracking the molecular intricacies of cancer metastasis, needed to find an animal model that worked. He hypothesized that maybe healthy prostate tissue - as well as cancerous tissue - was capable of sending growth signals to bone.

"There are only two animals in all of nature that get prostate cancer," says Rosol, "dogs and humans." Rosol says dogs and human have a lot in common. The canine prostate gland and its diseases are very similar to humans' 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.

"We were shocked," he says. Within two weeks, the density of the calvaria had just about doubled. "This was really exciting, not just because of the speed of the reaction, but because there are really very few things in nature that induce bone growth."

Rosol says it is not entirely clear what causes the bone to form, but added 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.

"We believe endothelin-1 plays a critical role, however," says Rosol, adding his research team is already working with a drug designed to block endothelin-1 activity, and it looks like it may be working.

The study is published in a recent issue of The Prostate.

Rosol says it is important to continue to develop new and workable animal models to better understand cancer. "With 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. We hope that discovery of the mechanisms of bone formation at sites of prostate cancer metastasis in bone will lead one day 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. "What is devastating for a prostate cancer patient may be a source of hope for someone with osteoporosis."

Ohio State University Wexner Medical Center

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