New research by scientists at the University of Michigan’s Comprehensive Cancer Center suggests that prostate cancer manipulates an important group of signalling proteins called Wnts (pronounced “wints”). “Normal bone growth and remodelling depends on a controlled balance between production of new bone and resorption of existing bone,” says Evan T. Keller, Ph.D., a professor of urology and pathology in the U-M Medical School. “When a tumour forms in bone, it upsets this balance.”
In the first phase of their research, the scientists measured the amount of Wnt protein in cells from normal human prostate tissue, localised prostate cancer and metastatic prostate cancer cells. Using the same cell lines, they also looked for the presence of a protein called DKK-1, which is known to inhibit Wnt activity. They discovered that the amounts of Wnt and DKK-1 protein present in human prostate cells varied inversely with the developmental stage of prostate cancer.
“Our results suggest that DKK-1 may act like a switch on prostate cancer cell activity,” Keller says. “When we altered the cells to increase the amount of active DKK-1, it blocked Wnt’s signal, changing prostate cancer cells from an osteoblastic to a highly osteolytic cell line.”
To test their hypothesis, U-M scientists injected human prostate cancer cells into the tibias, or long leg bones, of one group of immune-deficient mice. Twelve weeks later, U-M researchers removed and examined bone tumours from the mice. They found that these mice produced tumours with a dense overgrowth of bone.
A second group of mice, injected with prostate cancer cells made to express the Wnt inhibitor, DKK-1, developed highly osteolytic tumour lesions, which destroyed most of the bone. “This demonstrated that Wnts promote the overproduction of bone by prostate cancer cells,” Keller says.
MEDICA.de; Source: University of Michigan Health System