German researchers detail how metastatic cancer takes root in the brain

As many as one in four cancer patients develop metastatic cancers of the brain. Existing therapies seldom do more than slow the disease. Adding to the urgency to find a way to prevent brain metastasis is the increasing number of such cases.

"Improvements in the treatment of malignancy have enhanced survival time," said Dr. Frank Winkler, who leads the Neurooncology Research Group at the Ludwig-Maximilians-Universität (LMU) Neurological Clinic in Munich. "But this also means that more patients are at risk of developing brain metastases."

In the hope of finding ways to stop this process, Winkler and colleagues at LMU and neighboring Max Planck Institute for Neurobiology have defined, in animals, the steps that lead some tumor cells to metastasize. Reporting days before Christmas in the online version of Nature Medicine, Winkler and colleagues detailed the process of brain metastasis. To do so they used two-photon microscopy to look deeply into animal tissues and visualize at high resolution structures that lay hundreds of micrometers below the surface of the living brain.

The metastatic process begins, they found, when circulating tumor cells are trapped in a network of blood vessels. The cells then pass through tiny gaps between cells in the vessel wall, escaping into the surrounding brain tissue, yet sticking to the outer surface of the vessel. Here is where the process begins in earnest, as between four and fifty cells form micrometastases that ultimately fuse, triggering the growth of new blood vessels to feed the mass.

Interrupting any one of the steps will stop metastatic cancer in its tracks, according to Winkler. His team is now looking for ways to do exactly that. One may already be at hand. In their animal research, the team detailed how the anticancer drug Avastin can suppress the emergence of metastases by blocking the formation of new blood vessels. In the absence of such angiogenesis, even cells that had attached to the outer vessel wall and proliferated strongly at first eventually died, he says.

"We now want to test other types of cancer drugs for their effects on the single steps of metastasis formation," Winkler said. "It may be possible to discover new substances that allow us to treat existing metastases effectively, or even prevent them from developing at all."