Endostatin and Tumstatin Inhibit Angiogenesis in Different Ways

Researchers have found that two collagen-derived angiogenesis inhibitors prevent development of new blood vessels through different mechanisms, since endostatin binds to a5b1 integrin while tumstatin binds to aVb3 integrin.

Uncontrolled angiogenesis contributes to the pathogenesis of several diseases including psoriasis, rheumatoid arthritis, and diabetic retinopathy, as well as cancer. Working with endogenous protein fragments that are known to inhibit angiogenesis, investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) evaluated the functional receptors, mechanism of action, and intracellular signaling induced by endostatin and tumstatin. Their findings were published April 7, 2003, in the online edition of the Proceedings of the National Academy of Sciences.

"Just as aspirin, acetaminophen, and ibuprofen each work in different ways to relieve pain, it now appears that endogenous inhibitors like endostatin and tumstatin work in different ways to halt angiogenesis,” explained senior author Dr. Raghu Kalluri, associate professor of medicine at the Center for Matrix Biology at Beth Israel Deaconess Medical Center. "While human endostatin targets the endothelial cells' migratory abilities, human tumstatin prevents endothelial cells from proliferating. These two different approaches lead to the same outcome – halting the outgrowth of the blood vessels and inhibition of tumor growth. These findings may help us to be more informed in the ways we use these molecules as potential drug candidates in the future.”