Heparan Sulfate Linked to Tumor Growth and Metastasis

Cancer researchers have demonstrated a connection between heparan sulfate, a linear polysaccharide found in all animal tissues, and the ability of tumor cells to generate new blood vessels, which is required for growth and metastasis.

Investigators at the University of California, San Diego (UCSD; La Jolla, USA) created a model for studying the role of heparan sulfate by genetically engineering a line of mice that contained in their genome a mutation for the endothelial-targeted deletion of the biosynthetic enzyme N-acetylglucosamine N-deacetylase/N-sulfotransferase 1 (Ndst1). Lack of this enzyme caused a drastic reduction in the animals' heparan sulfate level.

Findings published in the April 30, 2007, online issue of the Journal of Cell Biology revealed that in the engineered mice generation of new blood vessels during cutaneous wound repair was unaffected, as was growth and reproductive capacity. On the other hand, formation of new blood vessels in experimental tumors was altered, resulting in smaller tumors and reduced microvascular density and branching. Binding of several metastasis-related growth factors was also considerably reduced in the engineered mice as compared to control animals.

"If novel drugs can be developed to target tumor heparan sulfate, we might be able to make a leap in cancer-fighting therapies, because several molecules critical to tumor endothelial growth also bind to heparan sulfate,” said first author Dr. Mark M. Fuster, assistant professor of pulmonary and critical care medicine at the University of California, San Diego. "Altering this binding would allow for suppression of a broader array of the tumor ‘fuels' for angiogenesis, without a major effect on normal vascular function.”


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