Tumor cells grow so rapidly they could outstrip their resourcesif they did not trigger new blood vessels to bring nourishment.
In an article in today's issue of Nature, scientists at GenentechInc. of South San Francisco, Calif., show that inhibiting newblood vessel formation suppresses the growth of tumorsinduced in mice. The group, led by Napoleone Ferrara, treatedthe mice with a monoclonal antibody to inactivate vascularendothelial growth factor (VEGF), a substance produced bytumors that spurs new blood vessel growth -- especially inareas starved for oxygen.
The monoclonal antibody did not halt the growth of tumor cellsin culture, but slowed tumor growth in immune-crippled"nude" mice. Tumors from treated mice also had fewer bloodvessels. The tumors were all induced with one of three celllines: human rhabdomyosarcoma, glioblastoma multiforme orlelomyosarcoma. Tumor suppression was greatest in the mostrapidly spreading malignancy, rhabdomyosarcoma.
VEGF is also believed to be involved in such healthy processesas wound healing, ovarian changes in pregnancy and embryogrowth. The factor "could be a major regulator of normal andpathological angiogenesis," Ferrara told BioWorld.
One of several factors being studied by different groups in ahighly competitive research area, VEGF acts only on the smoothendothelial cells that line the interior of blood vessels andother organs.
The research implies that tumors might be "starved" byblocking new blood vessel growth with a VEGF antagonist,Ferrara said. Most epithelial cells are quiescent in adults, headded, so blocking VEGF "could be a low-toxicity therapy."(Such an approach might impair reproduction, however, sinceendothelial cells do divide in the ovary and uterine lining.)
Ferrara added that VEGF might be used to enhance bloodsupply when existing arteries are blocked. New blood vesselsare known to form in thickened artery walls that carry plaquescreated by atherosclerosis. His group is already testing thehypothesis that VEGF plays a role in their formation.
Growth factors in heart disease were the subject of anaccompanying article about another growth factor with abroader spectrum of action. A group led by Gary Nabel at theUniversity of Michigan Medical Center in Ann Arbor introducedrecombinant acidic fibroblast growth factor into cultured pigarterial segments and demonstrated the hormone thickenedthe vessel wall and induced new capillaries. The Michigangroup suggested gene transfer of FGF-1 or related factors mightbe used in some heart conditions to improve blood flow.
-- Nancy Garcia Associate Editor
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