Bone marrow cells lodged throughout the body seed the development of metastases in mice, report Rosandra Kaplan and colleagues (Nature 438, 820–827). What's more, blocking a signal from the marrow cells can prevent the migration of metastatic cells to these locations.

The researchers first observed that bone marrow cells clustered at pre-metastatic locations before the arrival of tumor cells. These progenitor bone marrow cells were identified using markers typical of such cells. The cells also expressed vascular endothelial growth factor receptor-1 (VEGFR1), which seemed to be necessary for migration of metastatic cells. Shown is one such cluster of marrow cells (VEGFR1 in red, GFP-labeled marrow cell in green and DNA in blue).

It is unclear what causes the bone marrow cells to cluster in the first place. But in mice with tumors, expression of a protein that sticks to bone marrow cells, fibronectin, was somehow increased at organs that conventionally host metastatic tumors.

To show the involvement of VEGFR1, the researchers grew tumor cells in the presence of VEGFR1-expressing cells; as a result, the tumor cells adhered more strongly and divided more rapidly. VEGFR1 cells isolated from pre-metastatic clusters secreted growth factors, which may attract circulating tumor cells.

Finally, antibodies that blocked VEGFR1 completely prevented metastases in animals with established tumors. To date VEGF inhibitors have been used in clinical trials with the aim of thwarting angiogenesis and tumor blood supply. The findings suggest that they might be of use to block metastasis.