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Unexpected lock and key mechanism found for the assembly of tumor blood vessels

eveloping blood vessel, the interior area called the endothelia. The integrin was not produced in mature blood vessels, indicating a specific role in developing vessels. The team found that the integrin was produced in the endothelia of mouse and human blood vessels that feed tumors such as colon cancer, melanoma and lung cancer. Inhibitors of the integrin stopped new blood vessel growth and suppressed tumor growth, indicating that the integrin helped in the creation of tumors

"Our study marks the first time this integrin was found to play a key role in angiogenesis," said Varner. "This integrin is known to regulate the body's inflammation response, but until this study it wasn't suspected of regulating angiogenesis. It's possible that since the integrin only works on developing blood vessels and in cancer, disrupting its ability to form blood vessels could starve the tumor and stave off cancer."

The research team discovered that the integrin brought the endothelia, the inside part of a blood vessel, together to bind with vascular smooth muscle, the outer portion of a blood vessel. Blood vessels only work when both endothelia and vascular smooth muscle are bound together. Previous work on integrin alpha4beta1 showed that the protein worked in the immune system by binding with another molecule called VCAM, so the researchers next looked for evidence of VCAM in the vascular smooth muscle cells, called pericytes.

Indeed, Varner's team found VCAM on the nascent blood vessel's pericytes, but not in mature vessel pericytes. The two molecules, Varner discovered, work together to bring the endothelial cells together with the outer pericytes to create new intact blood vessels, with integrin as the lock and VCAM as the key. Drugs that inhibit either the integrin or the VCAM molecule prevented intact blood vessels from forming.

"When the integrin meets with VCAM, both cell types receive survival signals at this active sta
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Contact: Leslie Franz
lfranz@ucsd.edu
619-543-6163
University of California - San Diego
2-May-2005


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