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Laying bare the not-so-sweet tale of a sugar and its role in the spread of cancer
Date:4/25/2011

er VEGF-C and its receptor were getting any help from nearby molecules to make that happen. "After all, if there were other players in the mix, that might mean there are other possible drug targets," Fuster explains.

The team focused on a glycan, or sugar, known as heparan sulfate. After some initial clues indicated that destroying the unique sugar on lymphatic endothelial cells would inhibit VEGF-C-dependent growth signaling, Fuster and his team dug in to figure out more about heparan sulfate's role.

"In a cell-based system, we tried to interfere with the components that are involved in making heparan sulfate in lymphatic endothelial cells. We tried inhibiting the production of the sugar and destroying it," Fuster says.

Xin Yin, a postdoctoral research fellow, and Scott Johns, a research associate in the laboratory, both lead authors on the paper, carried out a variety of studies to examine how silencing enzymes in the cell that are responsible for putting the sugar together might alter various cell-growth behaviors and affect VEGF-C's ability to activate its receptor.

"What we found was that giving the glycan-altered cells the VEGF-C resulted in a blunting of the normal growth rate or signaling for growth," Fuster says. "This work shows there may be a key role for heparan sulfate in the initiation of lymphatic vessel-growth responses."

In the setting of cancer, it is thus possible that the presence of heparan sulfate is important for tumor-spurred lymphatic vessel growth: This not only identifies a potential target for anti-cancer drugs, Fuster says, but it may also offer insights about how to stimulate lymphatic vascular growth in diseased parts of the body that, conversely, need lymphatic vessels for normal circulatory and immune functions.

Still, though, Fuster emphasizes that more work remains to be done, because how exactly heparan sulfate interacts with VEGF-C and its receptor remains unclear: "Identi
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Contact: Angela Hopp
ahopp@asbmb.org
301-634-7389
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

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