Mesenchymal stem cells (MSCs) are a versatile group of adult stem cells known for their ability to repair injured tissue. They circulate in the blood like sentinels until they are called to sites of injury, where they differentiate into bone, cartilage, fat or muscle cells to repair or replace damaged tissue. Now, however, a team led by Robert Weinberg at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, has revealed a sinister side to MSCs. The researchers have shown that MSCs home not just to wounds but breast tumours, where they encourage the cancer cells to metastasize (or spread) to other tissues.

Research had already shown that MSCs derived from bone marrow are strongly attracted to the loose connective tissue that supports tumours1 and that MSCs infused into the blood in experimental animals localize to a variety of malignancies2,3. But their impact on the development and spread of tumours was poorly understood. Antoine Karnoub, first author on the paper, set out to explore the role of MSCs in cancer and discovered that these cells move into a breast tumour and 'educate' the cancer cells to metastasize. The work was published in a recent issue of Nature4.

Karnoub and his colleagues injected a mixture of human bone-marrow MSCs and human breast cancer cells subcutaneously into immunocompromised mice. Over 12 weeks, the mice developed malignant breast tumours, which metastasized to the lungs. The control group of mice injected with human breast cancer cells alone developed breast tumours but these did not spread.

So how were the MSCs exerting this effect? Karnoub et al. showed that MSCs at the tumour site release a small protein, the chemokine CCL5, that helps the breast cancer cells move. Indeed, metastasis could be halted by silencing the CCL5-mediated crosstalk between the two cell types.

These experiments are a significant advance in understanding how cancer spreads as they show both that environmental cues can influence whether a breast cancer cell will metastasize, and that this behaviour is reversible. CCL5 and its receptor may turn out to be important therapeutic targets in the fight against metastatic cancer.

Weinberg's team has yet to determine whether MSCs derived from other sources, such as fat, muscle or endothelial tissue, are similarly recruited to tumours and help their metastasis. However, a growing body of research suggests that MSCs derived from tissues as diverse as umbilical, adipose, muscle and liver have much in common, says Karnoub. Further research is also needed to determine whether MSCs interact with cancer cells in other ways or fuel a cancer's growth at secondary sites in bone.