When doctors discover high concentrations of regulatory T cells in the tumors of breast cancer patients, the prognosis is often grim（冷酷的，糟糕的） , though why exactly has long been unclear. Now new research at the University of California, San Diego School of Medicine suggests these regulatory T cells, whose job is to help mediate² the body's immune response, produce a protein that appears to hasten and intensify³ the spread of breast cancer to distant organs and, in doing so, dramatically increase the risk of death.

The findings are reported in the Feb. 16 advance online edition of the journal Nature.

The researchers found that mice with breast cancer were more likely to develop metastatic lung cancer due to elevated levels of RANKL, an inflammatory protein normally involved in bone remodeling. Regulatory T cells were found to be the primary source of RANKL in these tumors. However, the same increase in metastasis（新陈代谢） was seen when synthetic⁴ RANKL was injected directly into tumors, suggesting that RANKL was the key to the ability of regulatory T cells to promote the spread of breast cancer. The scientists also determined⁵ that interfering⁶ with the ability of RANKL to interact with cancer cells seemed to block tumor¹ progression, and may represent a potential target for drug therapy.

"What is exciting about this study is that now that we understand an increase in RANKL translates to an increase in metastasis, we can get to work on figuring out ways to stop or slow the production of RANKL in breast cancer patients," said Michael Karin, PhD, Distinguished⁷ Professor of Pharmacology and Pathology at UCSD's Laboratory of Gene⁸ Regulation and Signal Transduction and Moores Cancer Center.

RANKL is a well-known factor in a variety of degenerative bone diseases, including rheumatoid arthritis⁹（风湿性关节炎） and bone metastasis. In June 2010, the Food and Drug Administration approved the first RANKL-inhibiting drug for use in postmenopausal women at risk for osteoporosis.

"When we were able to control the RANKL production in the mice, we were able to slow or stop the spread of the cancer," Karin said. "The next logical step is to turn to drugs that block RANKL production to see how they might affect the spread of breast cancer."

Other breast cancer studies have linked RANKL to early stages in the development of synthetic progestin-driven breast tumors. According to the Women's Health Initiative and the Million Women Study, hormone¹⁰ replacement¹¹ therapy and contraceptives（避孕药） with progestin significantly increase the risk of developing breast cancer. The findings from these studies and the new UCSD research suggest that drugs that block RANKL may be effective in preventing both the early stages of breast cancer and the advanced progression of the disease.