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Snake venom studies yield insights for development of therapies for heart disease and cancer
Date:7/29/2010

planin, which binds to the CLEC-2 receptor protein on platelets, telling the platelets to get together and form a protective barrier around the cancer cells. Once enveloped, the cancer cells are not detected by the immune system and are able to bind to blood vessels' inner linings and spread, or metastasize, throughout the body," she explained.

Using a mouse model, the team in 2008 showed that blocking the tumor protein podoplanin from binding with the platelet receptor protein CLEC-2 could prevent tumors from metastasizing to the lung.

From snake venom to platelets to tumors

The recent investigations by the team, published in the JBC online July 4, hinged on the generation and study of genetically engineered mouse embryos that lacked the platelet receptor protein CLEC-2. In the end, the experiments showed that CLEC-2 is not only necessary for blood clotting but also necessary for the development of a different type of vessel, specifically lymphatic vessels that carry fluid away from tissues and prevent swelling, or edema.

"During fetal development, the CLEC-2 deficiency disturbed the normal process of blood clotting and, in fact, the normal development and differentiation of blood and lymphatic vessels," says Masanori Hirashima, an associate professor at Kobe University. "They had disorganized and blood-filled lymphatic vessels and severe swelling."

Podoplanin, Hirashima explains, is also expressed on the surface of certain types of lymphatic cells and is known to play a role in the development of lymphatic vessels: "These findings suggest that the interaction between CLEC-2 and podoplanin in lymphatic vessels is necessary for the separation between blood vessels and lymphatic vessels."

It has been known that tumors generate blood vessels to promote their growth, and it's possible that the formation of lymphatic vessels also may contribute to the spread of cancer throughout the body, says Osamu Inoue,
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Contact: Angela Hopp
ahopp@asbmb.org
301-634-7389
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

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