Even when dosed with drugs designed to freeze them in place, cancer cells still manage to spread through the body. A new finding may explain this baffling ability: The drugs themselves can cause cancer cells to revert to a primitive amoeboid state, allowing them to squeeze through the gaps between tissues. The discovery may one day lead to drugs that keep a tighter lid on tumors.
A tiny tumor can eventually devastate the body, if its cells invade other tissues. They do this by releasing protease enzymes that chew right through the walls of connective tissue that separate the tumor from the rest of the body. The fact that cancer cells can still migrate even when their protease enzymes are blocked with drugs suggests some alternative mode of travel. To catch them in the act, Peter Friedl of the University of Wuerzburg, Germany, and colleagues used video microscopy to spy on cancer cells embedded in artificial gels of collagen, similar to the connective tissue usually surrounding tumors. Their first film revealed the classic escape, with migrating cells nibbling telltale tunnels.
But the picture changed radically when protease blockers were added. Like the Blob of B-movie fame, the cells became amorphous, oozing with ease between fibers. "We were surprised!" says co-author Kata Wolf, whose original aim was to find a combination of protease inhibitors that would halt the cells. The shape-change also happened in an experiment with mouse skin, the team reports in the 20 January issue of the Journal of Cell Biology. Before drugs can be developed to target this amoeboid transition of cancer cells, says Friedl, its molecular mechanisms have to be worked out. The cause of the transmogrification remains a mystery.
The discovery is "completely unexpected," says Zena Werb, a cell biologist at the University of California, San Francisco. She would like to see if cancer cells can pull off the same trick in tissues other than skin, where they would be surrounded by a wider variety of cells.