Researchers at the University of Illinois have found that a molecular pathway known to have a role in the progression of bone cancer in humans is also critical to the pathology of skeletal tumors in dogs and cats. Their work could lead to advances in the palliative care of companion animals afflicted with osteosarcoma.

The research team, which included U. of I. pathobiology professor Anne Barger, examined the homeostatic role of an enzyme, receptor activator of nuclear factor kappa-B (known as RANK), and two key modulators of its activity: RANK ligand (RANK-L) and osteoprotegrin (OPG). RANK is one of a family of receptors that regulates bone and immune homeostasis. In health, RANK, RANK-L and OPG together keep the continual process of bone growth and resorption in balance.

Bone tumors presumably derail this homeostatic process, however, by upregulating RANK-L expression. RANK-L binds to RANK, stimulating the production and activation of osteoclasts (bone cells that increase the breakdown of bone tissue).

OPG counter-regulates RANK-L by blocking its ability to bind to RANK.

Eventual therapeutic interventions may make use of OPG or other RANK-L inhibitors to slow the process of bone destruction in skeletal tumors in cats and dogs, Barger said. Although not a cure, this could reduce the pain and other complications associated with bone cancer. Such therapies have proven effective at reducing pathologic bone loss in human bone cancer patients.

The researchers are the first to verify that the expression of this protein, which worsens the effects of bone cancer in humans, also occurs in cats and dogs with skeletal tumors. Their study appears in the January-February issue of the Journal of Veterinary Internal Medicine.

"Osteosarcoma is much more common in veterinary medicine than in human medicine," Barger said. "And in dogs it is fairly common."

Other studies have reported a tenfold greater incide
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Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
1-Mar-2007