Signaling protein shown to affect bone production in prostate Ca

Prostate cancer manipulates an important group of signaling proteins called Wnts to establish itself in bone, according to scientists at the University of Michigan's Comprehensive Cancer Center, Ann Arbor. By changing the amount and activity of the proteins, prostate cancer cells upset the normal balance between formation and destruction of bony tissue.

"There is strong evidence that Wnt proteins play a central role in regulating normal skeletal development in an embryo," said first author Christopher L. Hall, PhD. "But this is the first time Wnts have been shown to be involved in abnormal bone production in adult animals with prostate cancer."

In the first phase of their research, Dr. Hall and colleagues measured the amount of Wnt protein in cells from normal human prostate tissue, localized 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.

"As the cancer progressed, DKK-1 levels went down," Dr. Hall said. "Cells with osteoblastic activity had high levels of Wnt activity and low levels of DKK-1, while cells with osteolytic activity showed decreased Wnt activity and high levels of DKK-1."

The researchers then injected human prostate cancer cells into a group of immune-deficient mice. Twelve weeks later, they removed and examined bone tumors from the mice. They found that the mice produced tumors 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 tumor lesions, which destroyed most of the bone.

The study was published in Cancer Research (2005; 65:7554-60).