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Metastasis formation revealed in detail and real time
Date:12/20/2009

ogy in nearby Martinsried, Winkler and his collaborators Yvonne Kienast and Louisa von Baumgarten have, for the first time, been 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 study used two-photon microscopy, which allows one 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.

Different fluorescent markers were used to label blood vessels (in green) and the tumor cells (in red) which the team injected directly. By extending their observations over many weeks, the researchers discovered that metastasis formation requires four steps. First, circulating tumor cells must get trapped at a fork in the network of blood vessels. "In contrast to previous reports, intravascular growth is not sufficient to induce a metastasis", reports Winkler. "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.

It is the fourth step that gives the crucial signal for the development of a clinically relevant metastasis. This occurs when neighbouring micrometastases fuse and new blood vessels grow into the resulting mass. The latter process -- angiogenesis -- ensures that the tumor has a constant supply of nutrients, allowing it to grow unchecked. The imaging experiments also revealed the hurdles that cancer cells must overcome in order to form metastases. As Winkler points out, "Each one of the steps can go awry. Cells may not get out of the circulation, may fail to adhere to th
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Contact: Luise Dirscherl
dirscherl@lmu.de
49-089-218-02706
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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