NASHVILLE, Tenn. - An enzyme implicated in colon cancer may also play a role in other cancers by promoting development of blood vessels to feed tumors, a Vanderbilt-Ingram Cancer Center scientist and his colleagues report.
Writing in the June 1 issue of the Journal of Clinical Investigation, the researchers report that lung tumors in animal models grew at a slower pace when the gene for this enzyme (cyclooxygenase-2 or COX-2) was deliberately eliminated. In addition, tumor growth was significantly reduced by treatment with a drug to block COX-2 in animals that had the active COX-2 gene.
Upon closer examination, they found that, in the absence of COX-2, the tumors developed about 30 percent fewer blood vessels than those in the animals whose COX-2 gene was present and active. They also found that COX-2 levels were directly associated with levels of a growth factor that promotes the development of new blood vessels, a process called angiogenesis. In the cells missing the COX-2 gene, VEGF levels were substantially lower; with an active COX-2 gene, VEGF levels dropped after treatment with COX-2 inhibitors.
"It appears that the inhibition of tumor growth is due to lack of tumor-associated angiogenesis," said Raymond DuBois, MD, PhD, Mina Cobb Wallace Professor and Associate Director of Cancer Prevention at Vanderbilt-Ingram. "We are now examining exactly how that is controlled."
The link that is beginning to be established between COX-2 and angiogenesis - by these scientists and others - is important because it suggests selective COX-2 inhibitors might be useful as potential treatments for already established tumors.
Initially developed for arthritis, these drugs are similar to aspirin and non-steroidal anti-inflammatory drugs like ibuprofen. Aspirin and NSAIDs target both forms of the enzyme cyclooxygenase (1 and 2), both of which lead to the production of bio-active lipid hormones such as prostaglandins. Newer drugs, including the widely pre
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Contact: Cynthia Manley
cynthia.manley@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
23-May-2000