Abstract
Researchers have pinpointed a mechanism that links autoimmune arthritis with increased rates of invasive breast cancer in mouse models. The work suggests that interrupting the SCF-cKit signaling pathway and treating the arthritis may reduce metastasis to the lung and bone.
Targeting mast cells may help reduce and slow the spread of breast cancer into lungs and bone
Researchers from the University of North Carolina (UNC) in Charlotte have pinpointed a mechanism that links autoimmune arthritis with increased rates of invasive breast cancer in mouse models. The work implicates mast cells and the stem cell factor (SCF)-cKit signaling pathway, and suggests that interrupting this pathway and treating the arthritis may reduce metastasis to the lung and bone.
“Survival rates go down in women with both arthritis and breast cancer,” says Lopamudra Das Roy, PhD, research assistant professor at UNC, who is scheduled to present the findings at the American Association for Cancer Research Annual Meeting 2012 in Chicago on April 1. “There is a great need for new approaches to treatment because arthritis is very common among post-menopausal women.”
Das Roy previously found that autoimmune arthritis doubles the likelihood of bone metastasis and triples the likelihood of lung metastasis in mouse models of breast cancer.
In this new work, Das Roy studied 2 mouse models. One developed arthritis spontaneously and was induced to have breast cancer. The other developed breast cancer spontaneously and was induced to have arthritis. She then compared these mice to controls with induced and spontaneous breast cancer but no arthritis.
In the lungs and bones of arthritic mice, Das Roy found an increase in populations of mast cells, which are known to produce proinflammatory factors that promote invasive cancer. Das Roy also found an increase in SCF-cKit signaling.
Because mast cells express the cKit receptor, they increase SCF-cKit signaling. This sets up a “vicious cycle,” says Das Roy, because SCF-cKit signaling stimulates the production of more mast cells, which further promotes cancer.
By treating the arthritic mice with celecoxib—a U.S. Food and Drug Administration–approved drug for arthritis—and with an anti-cKit receptor antibody to block cKit in mouse mast cells, Das Roy significantly decreased metastasis and mast cell populations in lungs and bone.
To determine if this treatment has the potential to help humans, Das Roy now plans to examine mast cell populations in clinical samples of human breast cancer.
