To grow and spread, tumors need a steadily increasing blood supply.So do developing embryos.
The name of this game is angiogenesis _ proliferation of endothelialcells that build venules, arterioles and capillaries _ the vessels thattransport nutrient-bearing blood to burgeoning target tissues,malignant or benign. The master of the game is vascular endothelialgrowth factor (VEGF), which provides life support to tumors andembryos alike.
It takes two receptors to play. The VEGF protein can form bloodvessels in mouse and rat embryos (as well as in mammals generally)only after it latches on to its Flt-1 and Flk-1 receptors.
If a mutation inherited from both its parents' genomes disables eitherreceptor, the unborn mouse or rat dies in utero between days 8.5 and9.5 of gestation.
But, reports a paper in the April 4, 1996, Nature, "ligand[s] otherthan VEGF might activate such receptors."
Researchers at Genentech Corp., of South San Francisco, and theUniversity of Michigan, in Ann Arbor, disrupted the VEGF gene.Their article in Nature, titled "Heterozygous embryonic lethalityinduced by targeted inactivation of the VEGF gene," reports "theunexpected finding that loss of a single VEGF allele is lethal to themouse embryo between days 11 and 12."
Then, they injected embryonic stem cells lacking the VEGF gene intotumor-bearing nude mice. "The difference in tumor weight between[controls] and VEGF-minus clones was more than tenfold by fourweeks after injection," the researchers observed.
For lack of endothelial cells, the blood vessels were lost, andangiogenesis failed.
The same issue of Nature carries a parallel paper titled "Abnormalblood vessel development and lethality in embryos lacking a singleVEGF allele." It reports joint research by investigators at theUniversity of Louvain, in Belgium; the Max Planck Institute, BadNauheim, Germany and the University of Toronto. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.