Karmanos, Wayne State research to shed light on bone metastasis in prostate cancer
Tuesday, February 07, 2012
Prostate cancer is the most frequently diagnosed cancer in men and the second most deadly for them. A team of Barbara Ann Karmanos Cancer Institute and Wayne State University (WSU) researchers recently received $363,660 from the National Cancer Institute of the National Institutes of Health for the project — "Bone-induced c-kit in prostate cancer cells: implications for bone metastasis" — which aims to shed new light on implications for bone metastasis in prostate cancer.
As cancer grows in the prostate, cancerous cells can enter the bloodstream and spread to other parts of the body, particularly into the bones. These metastases are the primary cause of death in prostate cancer patients. Current treatments available for prostate cancer with bone metastases can only slow the growth of cancer cells or relieve symptoms.
According to R. Daniel Bonfil, Ph.D., associate professor of urology and pathology at Karmanos and WSU's School of Medicine and principal investigator of the project, the mechanisms by which prostate cancer cells take root and start growing once they become lodged in the bones are not well understood. In addition, Dr. Bonfil stated that cells respond to specific signals, or ligands, coming from the tissue where they are located through receptors usually expressed on their surface. When these receptors are activated by their specific ligands, changes in cell behavior occur.
"Our research aims to investigate the contribution of a receptor known as c-kit in the metastasis of prostate cancer to the bone," said Dr. Bonfil. "Through our previous research, we have reported for the first time that the expression of the c-kit receptor is augmented in bone metastasis of prostate cancer patients. We also observed that while c-kit is not produced in prostate cancer cells grown alone outside the body, the expression of the receptor is specifically turned on in the same cells when they contact bone cells either in vitro or in vivo, which implies a role for c-kit and its ligand in prostate cancer bone metastasis."
Dr. Bonfil and Hyeong-Reh Choi Kim, Ph.D., professor of pathology in WSU's School of Medicine, hypothesize that factors derived from the bone stimulate the production of c-kit and its ligand in prostate cancer cells, facilitating the growth and survival of metastatic cells to the bone, causing them to be less susceptible to chemotherapy.
Through genetic engineering, the team will modify the prostate cancer cells so they fail to produce c-kit. They will compare the growth of these cells within bone to control prostate cancer in which c-kit induction occurs, with the goal of determining the contribution of c-kit to bone metastasis. In addition, they will study the role of c-kit resistance to chemotherapeutic treatment.
"We anticipate that our research will shed light on a novel biological mechanism involved in bone metastasis, providing the foundation for the development of new tailored treatments that will eliminate morbidity and mortality due to this common complication in prostate cancer patients," said Dr. Bonfil.