Growth factor contributes to angiogenesis

January 29, 1999

ANN ARBOR—Because of its role in cancer and other diseases, many groups of researchers are trying to understand what influences and controls the process of angiogenesis (blood vessel growth). A University of Michigan team has found that a natural substance known as vascular endothelial growth factor (VEGF) contributes to angiogenesis not only by stimulating blood vessel growth, but also by prolonging the survival of blood vessel cells.
This finding has important implications for understanding how angiogenesis contributes to tumors and chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. It may also help researchers develop new strategies for treating angiogenesis-dependent diseases. The results appear in the February issue of the American Journal of Pathology.
Led by Peter Polverini, a professor in the School of Dentistry and the Medical School, the U-M group has been studying the relationship between angiogenesis and programmed cell death (apoptosis), a natural process essential for normal growth and development. Apoptosis is the process by which the body rids itself of cells it no longer needs—for example, worn out or damaged cells or cells that have done their jobs and are not longer needed. The researchers showed that VEGF protects blood vessel cells from cell death.
The U-M team first demonstrated this effect in culture dishes in which nutrients were reduced. Blood vessel cells in culture normally die when nutrient levels are low. But in the presence of VEGF they were able to survive, apparently because VEGF increases expression of a “survival gene” called Bcl-2. VEGF also induced the cells to organize themselves into vessel-like structures. After seeing this effect in cell culture, the U-M team developed a model system to study how human blood vessels behave inside the body. They mimicked the effect of VEGF by using cells engineered to constantly express the Bcl-2 gene. The engineered cells were first grown on sponges and then transplanted into mice. Again, the cells survived longer and formed more blood vessels than cells that had not been engineered to overexpress the Bcl-2.
The findings may help explain how blood vessels are able to proliferate around tumors—a toxic, oxygen-deficient environment that isn’t normally conducive to cell growth. Through the action of VEGF and Bcl-2, blood vessels are able to grow and survive in this environment, providing an uninterrupted supply of nutrients to the tumor. By understanding this mechanism, researchers may find new ways to starve tumors by inhibiting blood vessel growth.
Other researchers on the team were Jacques E. Nor, a doctoral student in Polverini’s lab; Joan Christensen, a health science research associate; and David J. Mooney, an associate professor with appointments in the School of Dentistry and the College of Engineering.
The work was supported by grants from the National Institutes of Health and CAPES (a Brazilian research organization that provides support to Nor).

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