New Study of Cancer in Mice Suggests Heparin-Related Sugars Curb Tumors

By LAURA JOHANNES
Staff Reporter of THE WALL STREET JOURNAL

CAMBRIDGE, Mass. -- Scientists at the Massachusetts Institute of Technology have found that injections of a sugar related to the common anticlotting drug heparin can sharply inhibit tumor growth in mice. The findings, published in Monday's proceedings of the National Academy of Sciences, suggest that heparin, now a generic drug made by several companies, could find use as a cancer treatment. The sugar tested by the MIT researchers is one of a family of molecules called heparan sulfates commonly found on cell surfaces throughout the body. It appears to work as a "molecular switch" for a wide variety of different cancers, said Ram Sasisekharan, an associate professor of bioengineering at MIT.

"The concept seems to be fairly universal," he said. So far, the sugar has slowed the growth of skin, lung and prostate cancers in mice, he added.

It isn't necessary to inject the tumor itself as the sugar appears to "home in" on the tumor, said study co-author Zachary Shriver, who works with Dr. Sasisekharan at MIT.

Dr. Sasisekharan's team found that different forms of heparan sulfate had sharply different effects on tumor cells. One form of the sugar actually speeded growth of the tumors and caused the cancer to spread throughout the body. Another related sugar, by contrast, slowed the growth of virulent skin and lung cancers. In unpublished work, the same antitumor effect was found in mouse prostate cancer, Dr. Sasisekharan said.

It is unclear whether heparan sulfates are as important in regulating human cancers as they are in mouse cancers. However, MIT is "actively in negotiations" with several potential collaborators, including a large pharmaceuticals company, about translating the discovery into a drug, said Dr. Sasisekharan, the paper's senior author.

Possible drugs include heparin, sold by Abbott Laboratories Inc., American Home Products Corp. and others, and an enzyme, called heparinase III, which is responsible for snipping larger sugars into the portion that appears to have the antitumor effect. Some scientists who work closely with heparin have long suspected that the drug might inhibit tumor growth. Although large clinical trials of a new form of heparin in the 1990s concentrated on clotting efficacy, the trials also showed a sharp reduction in mortality among cancer patients. Most scientists felt the collateral results were "a chance finding," said Jawed Fareed, a professor of pharmacology at Loyola University Medical Center in Maywood, Ill., and one of the nation's leading authorities on the drug.

Now, he says, it is clear that heparin should have been considered seriously as a cancer drug years ago. "The evidence and technique used by the MIT group is very convincing," he said. More data are needed, he cautioned, before doctors should consider giving the drug as a cancer treatment. Under U.S. Food and Drug Administration guidelines, physicians may legally give an approved drug for a nonapproved use, but pharmaceutical companies must market only approved uses of their drugs.

MIT's work arises from a detailed study of a few of the thousands of sugars which surround each cell in the body. These sugars have long been known to help cells interact with their environment. But until now, the role of these sugars in controlling cancer has been poorly understood.

What is probably happening on a microscopic level, Dr. Sasisekharan said, is that the different forms of heparan sulfate attach to different proteins depending on their structure. Those proteins, in turn, regulate cancer proliferation. There are probably several dozen cancer-inhibiting proteins, only a handful of which have been discovered to date, he added.

One such protein is endostatin, now being tested as a cancer treatment in human trials. Endostatin is believed to work by inhibiting formation of blood vessels in tumors. Previous research by MIT and its collaborators has shown that the protein does its work in part by attaching to a heparan sulfate fragment. That research, in conjunction with the newer findings, suggests that giving heparin or heparan sulfate might help make endostatin more potent, Dr. Sasisekharan said.