(photo credit: REUTERS)
When malignant melanoma – the most dangerous kind of skin cancer – spreads to the brain, it is almost always a death sentence. But now, Tel Aviv University researchers have found a way to detect micrometastases – tiny bunches of spreading cancer cells – months before they reach the brain and develop into fatal tumors.
The mechanisms that govern early metastatic growth and interactions of metastatic cells with the brain micro-environment have long remained shrouded in mystery.
According to the research led by Dr. Neta Erez of TAU’s pathology department and just published in Cancer Research, micro-tumor cells hijack astrogliosis, the brain’s natural response to damage or injury, to support metastatic growth.
This breakthrough could lead to the detection of brain cancer in its first stages and permit early intervention.
Erez and her team used mice to study and follow the spontaneous metastasis of melanoma in the brain. They recapitulated all the stages of metastasis – the initial discovery of melanoma in the skin, the removal of the primary tumor, the micrometastatic dissemination of cancer cells across the body, the discovery of a tumor and death.
The detection of metastasis depends on imaging techniques that still can’t detect micrometastases.
Melanoma patients whose initial melanoma was excised believe that everything is fine for months or years following the initial procedure.
But after the primary tumor is removed, micrometastatic cells learn to communicate with cells in their new micro-environment in the brain. These cells are at first hostile to them, but eventually, a tumor appears.
The cells traveled across the body to the brain or other organs but were undetectable at the micro level. When they become detectable, it is already too late for treatment.
Erez dubbed the period of the initial growth of disseminated micrometastatic cells in distant organs the metastasis’s “black box” – the history of melanoma in the brain. “We believe that we have found the tools to characterize this black box,” she said. “And this is key to developing therapeutic approaches that may prevent brain metastatic relapse. Every organ in the body has a defense system that detects intruders,” she explained. “Much of this is regulated by support cells in the brain. When there is tissue damage due to a stroke or viral infection, these cells are activated and induce an inflammatory response.
“At the earliest stages of metastasis, we already see astrogliosis and inflammation. The brain perceives the micrometastatic invasion as tissue damage, activating inflammation – its natural defense mechanism. We found that the inflammation unfortunately gets hijacked by tumor cells that are able to grow faster and penetrate deeper because the blood vessels in the brain are more permeable than in any other part of the body. We found that all of this happens very early on.”