A Wayne State University School of Medicine researcher was awarded a Department of Defense grant to continue her study into the connections between obesity and prostate cancer.

The Department of Defense’s $225,000 New Investigator Award will allow Izabela Podgorski, Ph.D., to continue her research into why prostate cancer cells migrate to the bones. Dr. Podgorski, an assistant professor of research in the School’s Department of Pharmacology, conducts her research in the laboratory of Dr. Bonnie Sloane. Her study, “Cathepsin K as a Link Between Obesity, Inflammation, and Prostate Cancer: Potential Therapeutic Implications,” is new research developed from her postdoctoral experience in proteases and bone metastasis.

Dr. Podgorski’s research focuses on metastasis of prostate cancer - the most common form of cancer in men in the United States - to the bone. In the advanced stage, she explained, prostate cancer cells spread from the prostate to other parts of the body, especially to the bones. Science has not yet discovered why bone is the most common site of secondary prostate cancers.

After cancer cells develop in the bone, they interact with cells within the bone marrow, disturbing normal function and leading to bone destruction. The osteoclasts (large multi-nucleate cells that reabsorb bony tissue) and cancer cells can produce special enzymes (proteases), which help degrade bone. Dr. Podgorski said one such enzyme, cathepsin K, is the only mammalian protease that can completely digest the main component of the matrix of bone. Cathepsin K is also known to play a role in the destruction of joints in patients with rheumatoid arthritis. Anti-cathepsin K drugs are being tested by pharmaceutical companies for treatment of osteoporosis.

Dr. Podgorski said obesity was recently identified as a factor contributing to development of prostate cancer, and obese men with prostate cancer are more likely to have aggressive tumors and to have cancer reoccurrences after surgery. Cathepsin K has recently been shown to be involved in formation of fat cells, which suggests another role for the enzyme in prostate cancer.

“The primary role of obesity in prostate cancer is still unclear and is a subject of many undergoing research projects,” she said. “One interesting feature about obesity is that it leads to an increased number of fat cells in the bone marrow, and fat cells can stimulate osteoclasts to destroy bone. Coincidentally, cancer cells prefer to metastasize to the parts of skeleton where osteoclasts are actively degrading bone, which suggests that fat cells in the bone marrow might be responsible for attracting prostate cancer cells to the bone.”

Dr. Podgorski will attempt to show that cathepsin K is involved in the growth of prostate cancer in bone not only by destroying bone matrix but also by mediating formation of fat cells and inflammation in bone marrow.

“We will also assess the involvement of fat cells and inflammatory cells in growth and aggressiveness of cancer cells,” she said. “Overall, these studies will determine whether the presence of cathepsin K in the bone promotes metastasis and whether this is due to involvement of this enzyme in formation of fat cells and inflammation in the bone marrow. We hope that ultimately findings of these studies will result in use of anti-cathepsin K drugs for treatment of advanced prostate cancer as well as identification of other potential targets for treatment of this disease.”