Hyaluronan Prevents Multidrug Resistance

Cancer researchers have found that small fragments of hyaluronan (hyaluronic acid) block the primary receptor for hyaluronan (CD44), which prevents initiation of a series of metabolic steps that enable cancer cells to develop resistance to chemotherapeutic drugs.

Hyaluronan is a polymer of disaccharides that are composed of D-glucuronic acid and D-N-acetylglucosamine, linked together via alternating beta-1,4 and beta-1,3 glycosidic bonds. Polymers of hyaluronan can range in size from 100 to 10,000 kDa. While it is found primarily in extracellular matrices, hyaluronan also contributes to tissue hydrodynamics, movement, and proliferation of cells, and participates in a number of cell surface receptor interactions, notably those including its primary receptor, CD44. Hyaluronan's contribution to tumor growth--stimulation of development of multidrug resistance--may be due to its interaction with CD44, which participates in cell adhesion interactions required by tumor cells.

Investigators at the Medical University of South Carolina (Charleston, USA) reported in the May 27, 2005, issue of the Journal of Biological Chemistry that treatment of cancer cells with fragments (oligomers) of hyaluronan prevented binding of the complete molecule to CD44. This action prevented the cancer cells from developing drug resistance. "Our work indicates that hyaluronan antagonists, for example small hyaluronan oligomers, reverse the malignant properties of cancer cells, including proliferation, invasiveness, and drug resistance, explained senior author Dr. Bryan Toole, professor of cell biology at the Medical University of South Carolina.

These results point up the potential importance of hyaluronan as a therapeutic target in multidrug-resistant carcinomas. "Hyaluronan oligomers are non-toxic, non-immunogenic, and readily applicable to several proliferative disease processes, especially cancer. We are hoping that hyaluronan antagonists can be used in conjunction with chemotherapy such that much lower and less toxic doses of chemotherapeutic agents can be used,” said Dr. Toole.”




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Medical University of South Carolina