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A lean and mean VEGF for cancer cells

More blood vessels sprout on cell clusters that fashion VEGF111 (bottom).

Cells that suffer DNA damage start pumping out a previously undiscovered version of the angiogenesis promoter VEGF, as Mineur et al. report. The variant, which is tough and mobile, might help cancer cells tap new sources of blood.

Researchers have already nabbed about 10 versions of VEGF, which many cancer cells overproduce to feed their need for blood. Mineur et al. were studying the effects of UV light on cells when they stumbled across another variant that lacks three of the eight standard VEGF exons. The new version, which the researchers dubbed VEGF111, forms in cells exposed to UV radiation or DNA-breaking compounds such as camptothecin. Those results suggest that the VEGF111 results from DNA damage.

VEGF111 is short but sturdy; it lacks the region that's vulnerable to protein-slicing enzymes such as plasmin, making it harder to break down. The variant is also missing the VEGF section that interacts with the extracellular matrix (ECM). That loss might boost VEGF111's mobility because it wouldn't get snared as it diffuses through the ECM.

The researchers didn't detect the new variant in cells from healthy mice and people, or in animals dosed with UV light or camptothecin, perhaps because the variant is rare. But tumor cells transplanted into mice that received camptothecin did manufacture VEGF111. To gauge the molecule's effects on angiogenesis, the team injected mice with tumor cells that fashioned one of three VEGF versions, including VEGF111. All three types of the growth factor spurred formation of new blood vessels. These vessels covered the tumors that made the two other VEGF isoforms, but they sprouted a short distance away from growths that produced VEGF111. The reason for this difference isn't clear.

Because it's durable and forms in response to DNA damage, such as that caused by chemotherapy, VEGF111 could be a formidable foe. It might help cancer cells resist drugs, for instance. On the other hand, the molecule could spur new treatments for conditions in which angiogenesis is desperately needed, such as heart attacks and nonhealing wounds.

Reference:

Mineur, P., et al. 2007. J. Cell Biol. 179:1261–1273.[Abstract/Free Full Text]

Mitch Leslie

mitchleslie{at}comcast.net

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This Article Full Text (PDF, 783K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Social Bookmarking                            What's this?