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Hyaluronan is one of the most abundant macromolecules of the extracellular matrix and regulates several physiological cell and tissue properties. However, hyaluronan has been shown to accumulate together with its receptors in various cancers. In tumors, accumulation of hyaluronan system components (hyaluronan synthesizing/degrading enzymes and interacting proteins) associates with poor outcomes for the patients. In this article, we review the main roles of hyaluronan in normal physiology and cancer and further discuss the targeting of hy
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