November 10, 2003

Prostate cancer collaboration earns $7.6M grant

By Vincent Dollard

Teamwork pays. A collaborative group of cancer researchers has won a $7.6 million grant from the National Cancer Institute to study the pathways and mechanism for prostate cancer   metastasis to bone. Titled "Prostate Cancer Bone Metastasis: Biology and Targeting," the collaboration consists of three separate but interrelated projects.

The overall project will be led by Leland Chung, director of research in the Department of Urology, and will bring together investigators from the School of Medicine (departments of urology, pathology and biostatistics), Winship Cancer Institute and the Rollins School of Public Health. In addition, researchers from the University of Dela-ware, University of Virginia, Stanford University and the Fred Hutchinson Cancer Research Center will participate.

"The strength of this project is its interactive nature," said Chung, a Georgia Cancer Coalition Distinguished Scholar. "We are all looking at different parts of the metastasis problem, and the laboratory activity is highly interactive. This project is organized to achieve synergy among individual scientists who have an established track record of research collaboration."

Nearly 90 percent of all prostate cancer patients who die from the cancer experience bone metastasis. "The ultimate goal of this project," Chung said, "is to develop novel diagnostic, prognostic and treatment options based on a better understanding of the mechanics of prostate cancer and bone metastasis."

The three primary projects are:

"The Biology of Tumor-Stroma Interaction," led by Chung, will study the interaction between metastatic human prostate cancer cells and bone or prostate stroma, which contributes to localized cancer growth, invasion and distant metastasis. The purpose is to develop potential molecular or genetic targeting strategies for treatment of prostate cancer bone metastasis.

"Heparan Sulfate Proteogly-cans in Prostate Cancer Bone Metastasis," led by Mary Farach-Carson from the University of Delaware, will study the interactions between prostate cancer cells and the marrow stromal cells that facilitate the progression of metastases in bone and bone marrow. By better understanding the bone stromal "microenvironment," researchers predict a better understanding of how metastasis occurs within the bone, which should lead to development of novel therapeutic strategies for disrupting that process.

"Mitochondrial DNA Mutations in Prostate Tumorigenesis and Stromal and Epithelial Interaction," led by John Petros, associate professor of urology at Emory, will research mitochondrial DNA mutations in prostate cancer to determine how those mutations protect cancer cells from normal cell death and enhance tumor growth and metastasis, and how cancer-associated stromal cells may support the survival of cancer cells.

In addition, the grant will involve three "core groups" that will provide biostatistics, animal and tissue cultures, and pathology and laboratory support.

Chung said an important goal of the three collaborative projects is to discover relevant genes that may "turn on or turn off" during the making of prostate cancer cells and their subsequent metastasis to bone.

"This collaboration enables us to validate laboratory findings using animal and tissue culture models with well-documented clinical specimens," Chung said. "By embarking on this team approach to the problem of prostate cancer bone metastasis, we may discover new pathways that support the metastasis. As a result, new therapies may be generated in the diagnosis and treatment of men with advanced forms of prostate cancer."