Once a tumor reaches a certain size, it must develop a blood supply in order to grow larger. Thus, understanding how new blood vessels grow (angiogenesis) and how to stop the process, could lead to treatments for cancer.
Proteins called integrins are now known to be crucial to angiogenesis. Integrins consist of alpha and beta subunits that connect the interior of a cell to the extracellular matrix. Antibodies that bind to integrins and block their activity have been shown to inhibit the formation of new blood vessels in animal models, and one integrin inhibitor, Vitaxin, is now in human trials. However, there are many different types of integrin, and a new report in Nature Medicine (Vol. 8, No. 1, p. 27, 01 Jan 02) shows that defining precisely which of these proteins are involved is crucial to developing an effective drug.
The hypothesis goes that if integrins are important to the growth of new blood vessels, one would predict that angiogenesis is impeded in their absence. However, Kairbaan Hodivala-Dilke and colleagues at the Imperial Cancer Research Fund, London, report that mice lacking beta3 integrins or both beta3 and beta5 integrins (which both belong to the alpha-v class) not only grow properly, but still develop new tumors with even more enhanced angiogenesis than normal mice. This obviously suggests that these integrins are not essential to angiogenesis. The drug Vitaxin binds to the alpha-v beta3 integrin.
In an accompanying News & Views article (p. 14), angiogenesis expert, Peter Carmeliet of Flanders University, Belgium, writes, "Although these findings do not dispute the therapeutic potential of anti alpha-v beta3 antagonists, they challenge our notion that integrins only enhance angiogenesis. A better understanding of integrin action might improve efficacy and safety of ongoing clinical anti-angiogenesis trials."
Dr. Kairbaan M. Hodivala-Dilke
Imperial Cancer Research Fund
St. Thomas' Hospital
Tel: +44 20 7960 5826
Fax: +44 20 7922 8216
Dr. Peter Carmeliet
Center for Transgene Technology and Gene Therapy
Flanders Interuniversity Institute for Biotechnology
Tel: +32 1634 5772/4
Fax: +32 1634 5990
(C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza