The researchers didn't find any lung tumor metastases in mice without lymphocytes. Yet, when RANKL was injected into the animals, the same potential for the cancer to spread was restored, indicating that the lymphocytes, which make RANKL, are critically important to the process.
"Without lymphocytes, there is no metastasis," said Tan. "If we treat the mice with RANK ligand, there are metastases, which indicate that RANK ligand can compensate for the function of lymphocytes."
The study establishes the role of RANKL-expressing lymphocytes as a promoting factor in breast cancer metastasis and provides a potentially good marker for breast cancer prognosis, the researchers said.
Tan noted that additional experiments showed that blocking both RANKL and IKK alpha in those breast tumor cells inhibited lung metastases. "More importantly," he said, "blocking the signaling pathway downstream of RANKL blocks primary metastasis and can potentially be developed as a treatment strategy."
Results such as these are helping to change the thinking about inflammation and cancer. "In general, we used to think that inflammation in the immune response is a part of the host defense against the tumor, but now we think that there are different kinds of inflammation," Tan said. "For example, T-helper cells can activate an anticancer response, but can also promote a separate tumor promoting response. In this study, if we target the host pro-tumor inflammation and immune response, we can also reduce tumor metastasis and are very likely to develop a therapy that is more effective."
|Contact: Steve Benowitz|
University of California - San Diego