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Dual effect on tumor blood vessels
Date:5/31/2012

As soon as they have grown to pinhead size, tumors rely on the formation of new blood vessels a process which is scientifically called angiogenesis. Interfering with this process (antiangiogenesis) is considered to be a promising approach in cancer medicine. However, those drugs that are already available for preventing the sprouting of new blood capillaries have failed to fulfill the high expectations placed on them.

Medical researchers hope to increase the efficacy of antiangiogenic therapies by attacking angiogenesis from several angles. Currently available antiangiogenic drugs are directed against the VEGF growth factor, which induces the sprouting of new blood vessels. However, other important players in angiogenesis include two signaling molecules called angiopoietin-1 and angiopoietin-2. Ang-1 is responsible for vascular maturation, while Ang-2 is a functional antagonist of Ang-1. Both signaling molecules bind to the same receptor, Tie-2, on the surface of endothelial cells.

"There are already studies showing that Ang-2 is a suitable target of new therapies directed against the blood supply of tumors. Combinations with already approved antiangiogenic drugs are regarded as particularly promising," says Prof. Dr. Hellmut Augustin, whose working groups are located at DKFZ and at Medical Faculty Mannheim of the University of Heidelberg. "However, as the role of Ang-2 was not entirely clear yet, we first needed to gain a better understanding of its molecular mechanism of action."

The scientists in Augustin's group have now found out that epithelial cells at the tip of sprouting capillaries produce large amounts of Ang-2, but not its known receptor, Tie-2. Nevertheless, these cells respond to the signaling molecule. This has prompted researchers to conclude that Ang-2 may also be able to mediate signals to epithelial cells via other surface molecules than Tie-2.

Indeed, the team of vascular experts found in the tip cells of
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Contact: Dr. Sibylle Kohlstaedt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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