New model of prostate cancer helps identify promising pain treatment

December 01, 2005

COLUMBUS , Ohio - Researchers have developed a new line of prostate cancer cells that they hope will provide a better model to study the disease.

This new cancer-cell line has already provided some help. One new study in mice identified a promising possible therapy to reduce skeletal pain that accompanies prostate cancer. Scientists found that a substance called anti-nerve growth factor appeared to be more effective in controlling pain in mice than even morphine.

But the work would not have been possible without the new cell line, said Tom Rosol , a study co-author and a professor of veterinary medicine at Ohio State University.

Armed with this new cell line, scientists will be able to more directly study how prostate cancer affects the body, said Rosol, whose laboratory developed the cell line.

Metastatic bone tumors are a common manifestation in patients with late-stage breast cancer or prostate cancer. "Metastasis" means that cancer has spread from its original site to other areas of the body. But breast cancer typically destroys bone at tumor sites, whereas prostate cancer tumors that spread to bone induce abnormal bone growth.

Currently, most models used to study prostate cancer do not mimic the human condition and the resulting bone metastases. Most of these models really mimic the spread of breast cancer since the bone metastases in that disease are associated with bone loss rather than bone growth.

"Even though there is more bone at the sites of prostate cancer tumors, this formation still damages the bone," said Rosol, who is also dean of the College of Veterinary Medicine at Ohio State . "The new growth compresses nerves, making it terribly painful for the patient."

The results appear in a recent issue of the journal Cancer Research. The study was led by Patrick Mantyh, a professor of preventive sciences at the University of Minnesota.

Only two mammals are known to develop prostate cancer -- men and dogs. Rosol's laboratory created a cell line from prostate tumors that had developed in a dog's bones. The researchers call this line of cells ACE-1.

In the current study, researchers at the University of Minnesota injected the ACE-1 cells directly into the femurs, or thigh bones, of male mice. These mice were specially bred to lack an immune system, leaving them vulnerable to developing prostate cancer. While the femur is the biggest bone in the body -- and therefore the easiest to study in this case -- prostate cancer can affect any bone in the body.

It took about a week for the prostate tumors to develop in the mice. At that point, the researchers began treating mice with anti-nerve growth factor (NGF). Anti-NGF is a molecule that naturally occurs in the body, where it promotes the survival and growth of nerves. An additional group of mice was treated with morphine. Control mice, which also had prostate cancer, were given a sterile saline solution instead of either anti-NGF or morphine.

The researchers wanted to know what kind of effect, if any, anti-NGF had on pain-related behaviors, tumor growth, bone formation and bone destruction in the mice.

The researchers watched mice at different points in the study to see if they showed any kind of pain-related behavior. The researchers kept track of how much time each mouse spent favoring its affected leg - how often the mouse lifted its leg while standing still, and for how long it held this leg aloft.

Mice treated with anti-NGF spent less time favoring their affected leg than did mice that were given morphine. In some cases, the time that a mouse treated with anti-NGF spent favoring its affected leg was half that of a mouse treated with morphine.

This suggests that anti-NGF therapy may be effective in reducing pain, thereby helping to enhance the quality of life in patients with bone pain caused by prostate cancer.

All of the animals were euthanized about two weeks after receiving the first round of ACE-1 injections. At that point, the researchers removed the affected thigh bone from each mouse in order to analyze the bone's density. Bone density corresponded with the number of tumors in the bone - the denser the bone, the more tumors it had.

Results from the density analysis showed that anti-NGF therapy did not stop prostate cancer from progressing, nor did it decrease bone formation caused by the disease.

Why prostate cancer causes excess bone to form remains a mystery, but having the ACE-1 model may help researchers learn why it happens.

"Bone is often the only clinically detectable site of the spread of prostate cancer," Rosol said. "Understanding why this happens is not only important for cancer patients, but also for scientists who are trying to understand how bone responds to different biochemical factors."
-end-
Rosol conducted the study with researchers from the University of Minnesota; the Veterans Affairs Medical Center in Minneapolis; and with Rinat Neuroscience Corporation, in Palo Alto, Calif.

This work was supported by a grant from the National Institutes of Health, the MinCREST program at the University of Minnesota and a Merit Review from the Veterans Administration.

Written by Holly Wagner, (614) 393-8310; Wagner.235@osu.edu

Ohio State University

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