Dr. Sloane's work could prevent cancer metastasis to bone.

One of the primary dangers of prostate cancer is that it can spread to the bones. Once there, the cancer eats away at the bones, making them more and more prone to fractures.

Bonnie Sloane, PhD, is conducting research to discern the roles of two enzymes, called cathepsins B and K, in this bone degradation and to determine whether the cancer cells are inducing that activity. Chair of the WSU pharmacology department and head of the protease program in the Karmanos Cancer Institute, Dr. Sloane is conducting her work under a three-year, $560,000 grant from the Department of Defense.

The study on the enzymes’ association with bone degradation was a natural for Dr. Sloane, who has been studying cathepsins and their part in cancer progression for many years. She was also spurred by a previous genomics effort through the National Cancer Institute that found that premalignant lesions to prostate cancer were already exhibiting heightened expression of cathepsin B. She explained, “Cathepsin B is expressed in a lot of cells, but it’s upregulated in tumors, and it’s upregulated by numbers of mechanisms, including amplification of the genes.”

Cathepsin K was another story. “Cathepsin K, in contrast, is expressed in just a few cells, and it is expressed very highly in osteoclasts,” Dr. Sloane said. Osteoclasts are large cells that are involved in the degradation of bone in such conditions as osteoporosis and arthritis. “We’re hypothesizing that cathepsin K might be involved in bone degradation induced by the metastatic tumors.” Although she and her research group don’t yet have direct evidence for the hypothesis, she noted that cathepsin K has at least one unusual property than gives credence to the notion: “This particular enzyme, unlike a lot of enzymes, is able to degrade type I collagen, which is the organic matrix of bone.”

For the next step, they will look for expression of both cathepsins B and K in tumor cells and then investigate whether the tumor cells have the ability to change the expression of the two enzymes in osteoclasts within the bone.

She noted that their findings might ultimately have an impact not only on prostate cancer, but breast and other cancers that metastasize to bone. Dr. Sloane is professor and chair of pharmacology.