Where Do Breast Cancer Cells Hide?

One the great challenges of achieving the goal of curing patients with breast cancer is to eliminate dormant tumor cells that can manifest as recurrent disease even many years after diagnosis and treatment of early disease. The bone microenvironment has been thought of as a sanctuary site for dormant tumor cells. Bone marrow (BM) micrometastases have been detected in up to 30% of patients who have stage I–III disease with no clinical evidence of metastatic disease, and these patients are known to have a worse prognosis than their counterparts without BM involvement. Additionally, circulating tumor cells have been detected in the peripheral blood of a fraction of patients with early-stage breast cancer following removal of the primary tumor.

The trafficking of tumor cells between the BM and the peripheral blood has not been previously elucidated. But now, investigators have used high-resolution, real-time fluorescence microscopy to track breast cancer cells (BCCs) in an animal model and give us a clearer picture of the niche, or hiding place, for these cells in the BM and of the molecular controls that regulate movement between the compartments.

The researchers found that BCCs in the BM reside predominantly in E-selectin and stromal cell–derived factor 1 (SDF-1)-rich perisinusoidal vascular regions. E-selectin is a cell-adhesion molecule that is present on the lumen of specialized vascular beds in the BM. By using specific inhibitors to E-selectin and SDF-1, the investigators were able to show that E-selectin is key to allowing BCCs to pass through the vasculature into the BM microenvironment, while the SDF-1 interaction allows for anchoring of the BCC to the BM microenvironment. Other investigators have shown that BCCs losing the interaction with the BM microenvironment quickly become apoptotic.