Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12

Abstract

Metastasis: brain metastases fuel further spread Breast cancer metastases to the brain secrete signaling molecules that promote additional cancer cells to migrate there. Peter P. Lee and colleagues from the City of Hope in Duarte, California, USA, analyzed protein and gene expression levels in brain metastases, and showed that it is the stromal cells (support cells such as fibroblasts), rather than the cancer cells themselves, that are the source of these homing signals. When compared against stromal cells derived from primary breast tumors or healthy breast tissue, they found that the stromal cells that had lodged themselves in the brain expressed the highest levels of CXCL12 and CXCL16, two chemokines involved in cell movement. Using three-dimensional aggregates, the researchers showed that these metastatic stromal cells promoted cancer cells migration more potently than stromal cells from primary tumors or normal breast tissues. Blocking the chemokine activity or that of its receptor impaired cancer cell movement, suggesting a possible therapeutic strategy for preventing brain metastasis in patients with breast cancer. These results highlight the importance of the tumor microenvironment and stromal cells in the metastasis process of breast cancer.