A growing tumor is considered by its surrounding normal tissue to be a bit like a wound. As also occurs during the wound response, tumors recruit mesenchymal stem cells (MSCs)—which are meant to help with repair—from the bone marrow. Karnoub et al. hypothesized that these MSCs, rather than being helpful, may instead advance disease. To investigate this idea, they injected human breast cancer cells, either alone or along with human MSCs, into mice and then looked for metastases in the animals' lungs.
When MSCs were mixed with tumors, several cancer cell lines were more metastatic. This behavior was reversible; MSC-induced metastases purified from one animal and then injected without MSCs into new animals were no more metastatic than the original primary tumors. MSCs thus seem to teach cancer cells tricks that are not intrinsic to the cancer itself.
Some of these tricks might be learned from MSC-derived chemokines. The MSCs provided two lines of breast cancer cells with the chemokine CCL5, which caused the tumor cells to become more motile and invasive. MSCs had to contact cancer cells to make CCL5, but it is not known what interactions are important. And not every cancer line stimulated CCL5 production. “I liken it to a key-and-lock situation,” says Karnoub. “The cancer has the key, but what lock it fits to release CCL5 from MSCs is a mystery.”
Karnoub is also interested in how cancer cells cause long-term changes in MSC behavior. “The MSCs remembered having been in contact with tumor cells; even three days or more after their initial exposure, they were still making CCL5. There's a two-way communication going on there.”