Changing Cancer Cells' Surface Sugars Can Inhibit Tumor Growth

The key to halting cancer cells may lie in their sugary coats, scientists say. Carbohydrate
molecules surround all cells and help them to identify and interact with one another. Now
new research, published today in the Proceedings of the National Academy of Sciences,
indicates that altering some of the surface sugars associated with cancer cells can control
tumor growth. The findings suggest that the sugars could one day serve as targets for new
anti-cancer therapies.

Previous research had suggested that certain features of the polysaccharide sugars
surrounding tumor cells might indicate either the stage or aggressiveness of the cancer.
Whether changes to the coating were a cause or a consequence of the disease, however,
remained unclear. To investigate the control a cancer cell's sugar jacket exerts over its
growth, Ram Sasisekharan and colleagues at the Massachusetts Institute of Technology
employed two enzymes capable of cutting the sugar heparan sulfate in different places.
They injected cancerous mice with both the enzymes and the two sugar fragments they
produce. Injection of heparinase 1 (hep 1) or its corresponding sugar fragment promoted
growth of melanoma tumors in the mice. Injection of heparinase III (hep III) or its
product, in contrast, inhibited tumor growth and prevented spread of the disease to other

The researchers also investigated the mechanism by which the two sugar fragments act
on cancer cells and determined that the sugars bind to, and hence disrupt, the activity of
certain signaling molecules involved in tumor activity. The opposing effects that the two
molecules have on tumor growth suggest that cancer could involve a biological balancing
act. "Tumors might be kept in check by the body's production of specific enzymes that in
turn release sugar fragments that keep tumor cells dormant," Sasisekharan explains. "Or,
perhaps in response to pathophysiological changes, a tumor cell releases different
enzymes that enable the tumor to grow more rapidly." —Sarah Graham