Natural Angiogenesis Inhibitors Slow Tumor Growth

A recent report described the role played by naturally occurring inhibitors of angiogenesis (formation of new blood vessels) in the suppression of tumor growth.

Investigators at Harvard Medical School (Boston, MA, USA) used lines of mice genetically engineered to lack the genes for the endogenous angiogenesis inhibitors tumstatin, endostatin, or thrombospondin-1 (TSP-1). A fourth line of mice lacked the genes for both tumstatin and TSP-1.

They found that normal physiologic levels of these inhibitors served to retard the growth of tumors, and that their absence led to enhanced angiogenesis and a two- to three-fold increase in tumor growth. Tumors grew twice as fast in the mice lacking both tumstatin and TSP-1, compared with either the tumstatin- or the TSP-1-deficient mice.

A fifth line of mice was engineered to overexpress the gene for endostatin, a situation mimicking human Down syndrome where the extra chromosome 21 produces about 1.6 times more endostatin than in normal individuals. Tumors in humans with Down syndrome are known to grow at an especially slow pace. Results of the current study published in the February 14, 2005, online edition of the Proceedings of the [U.S.] National Academy of Sciences showed that tumors in this group of mice grew three times more slowly than did tumors in normal mice.

"Between nine and 10 million people worldwide die of cancer each year,” said senior author Dr. Raghu Kalluri, associate professor of medicine at Harvard Medical School. "While a lot has been learned of how genetic defects convert normal cells into cancerous cells, much less is known about how the body defends itself against the growth of cancer. Our study helps provide a glimpse into what may be happening. The hope is that this new understanding of cancer growth can eventually lead to the use of these natural proteins as therapies to treat cancer at an early stage, before it becomes a devastating disease.”




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