A mechanism behind brain metastases of cancer patients has been identified, say scientists from LMU Munich.
Led by neurologist Dr. Frank Winkler, the research team followed, in real time, the steps that lead some tumour cells to establish metastases, while others fail to form new tumors.
AdvertisementThey discovered that, by blocking formation of new blood vessels, the anti-cancer drug Avastin could suppress the emergence of metastases.
"We hope that our results will help to optimize existing therapies and allow us to develop new agents that can be targeted against specific stages in the process of metastasis," Nature quoted Winkler as saying.
It is not the primary tumour that kills most cancer patients, but the metastases which arise from it.
Metastases in the brain are associated with a particularly dismal prognosis. These secondary tumours frequently appear in patients who have, or have had, lung, breast or skin cancers. They are very difficult to treat, as existing therapies can only slow, not cure, the disease.
During the study, research team was able to follow the fate of single cancer cells, in real time, over periods long enough to allow the development of large metastases in the brain.
The use of two-photon microscopy allowed them to look deeper into tissues than is possible with conventional fluorescence microscopy.
The technique can visualize, at high resolution, structures that lie hundreds of micrometers below the surface of the living brain.
"Essentially, we were able to monitor the stages of metastasis formation live", remarks Yvonne Kienast, from Max-Planck Institute for Neurobiology
Different fluorescent markers were used to label blood vessels and the tumor cells which the team injected directly.
They discovered that metastasis formation requires four steps. First, circulating tumor cells must get trapped at a fork in the network of blood vessels.
"We observed that such cells must then escape into the surrounding tissue by passing through tiny gaps between the cells of the vessel wall. In the third step, they have to stick to the outer surface of the vessel, where micrometastases, consisting of four to fifty cells, can develop," said Winkler.
It is the fourth step that gives the crucial signal for the development of a clinically relevant metastasis.
The researchers said that many cancer cells can remain in a resting state for long periods, and then suddenly begin to grow again.
"This is why metastases often appear years after successful therapy of the original tumor", he says. It turns out that direct contact with a blood vessel is also essential for the survival of resting tumor cells. These new findings should soon contribute to improving patient care," Wrinkler added.
The study appears in journal Nature Medicine.
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