The extracellular matrix is part of the microenvironment and its functions are associated with the physical and chemical properties of the tissue. Among the extracellular components, the glycosaminoglycan hyaluronan is a key component, defining both the physical and biochemical characteristics of the healthy matrices. The hyaluronan metabolism is strictly regulated in physiological conditions, but in the tumoral tissues, its expression, size and binding proteins interaction are dysregulated. Hyaluronan from the tumor microenvironment promotes tumor cell proliferation, invasion, immune evasion, stemness alterations as well as drug resistance. This chapter describes data regarding novel concepts of hyaluronan functions in the tumor. Additionally, we discuss potential clinical applications of targeting HA metabolism in cancer therapy.
Keywords: CD44; Cancer Stem Cells; Cancer therapy; DNA damage; Drug Resistance; Extracellular Matrix; Hyaluronan; Hyaluronan Synthases; Hyaluronan metabolism; Hyaluronidases; Immune response; Stemness; Tumor microenvironment; Tumor-Associated Macrophages; UGDH.