Turncoats in the battle against cancer

August 31, 2009

They are supposed to be the standard bearers of the body’s defense against disease. But when it comes to cancer, some macrophages are traitors, helping rather than fighting the enemy. They attach to metastatic tumor cells, as they do to other threats. But rather than destroying metastatic cells, these macrophages enable their growth.

They are supposed to be the standard bearers of the body's defense against disease. But when it comes to cancer, some macrophages are traitors, helping rather than fighting the enemy. They attach to metastatic tumor cells, as they do to other threats. But rather than destroying metastatic cells, these macrophages enable their growth.

For now, the results have been found only in mice. But the researchers who documented this effect believe it is not restricted to rodents.

"Macrophages, or their unique signaling pathways, represent new therapeutic targets that may be efficacious in reducing cancer mortality," said Jeffrey W. Pollard, PhD, deputy director of the Cancer Center at the Albert Einstein College of Medicine of Yeshiva University.

Pollard, a professor of developmental and molecular biology at Einstein, analyzed the movement of breast cancer cells in mice, finding that certain macrophages help these cells establish malignant outposts distant from the primary tumor. Because metastatic disease resists chemotherapy and radiation treatments, it is the major cause of cancer mortality. If metastasis could somehow be blocked, the impact on cancer mortality would be enormous, Pollard said.

The research at the Einstein College of Medicine could go a long way toward doing making that happen. Work already completed there shows that metastatic tumor growth in mice is inhibited if these particular macrophages are killed. This is so even after breast cancer cells have lodged in the animals' lungs and started to grow aggressively.

Macrophages typically alert other immune cells to infection, helping to identify viruses and bacteria that need to be killed. But the Albert Einstein study (published Aug. 17 online in PLoS ONE) definitively shows the pro-cancer effects of macrophages at distant sites and identifies the type of macrophages responsible for this treason, Pollard said.

"This is the first proof that they have impact at this location, at the site of metastatic tumor growth," he said.

Previous research by Pollard and colleagues demonstrated that macrophages also promote the growth of primary tumors. Finding a way to take these traitors out, therefore, could be a powerful weapon against cancer.