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Dissecting the role of hyaluronan synthases in the tumor microenvironment
Author(s) -
Passi Alberto,
Vigetti Davide,
Buraschi Simone,
Iozzo Renato V.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14847
Subject(s) - glycosaminoglycan , tumor microenvironment , hyaluronic acid , angiogenesis , microbiology and biotechnology , hyaluronan synthase , stroma , cancer cell , sulfation , chemistry , intracellular , receptor , cell , cell growth , cancer , biology , biochemistry , cancer research , extracellular matrix , immunology , genetics , immunohistochemistry
The tumor microenvironment is becoming a crucial factor in determining the aggressiveness of neoplastic cells. The glycosaminoglycan hyaluronan is one of the principal constituents of both the tumor stroma and the cancer cell surfaces, and its accumulation can dramatically influence patient survival. Hyaluronan functions are dictated by its ability to interact with several signaling receptors that often activate pro‐angiogenic and pro‐tumorigenic intracellular pathways. Although hyaluronan is a linear, non‐sulfated polysaccharide, and thus lacks the ability of the other sulfated glycosaminoglycans to bind and modulate growth factors, it compensates for this by the ability to form hyaluronan fragments characterized by a remarkable variability in length. Here, we will focus on the role of both high and low molecular weight hyaluronan in controlling the hallmarks of cancer cells, including cell proliferation, migration, metabolism, inflammation, and angiogenesis. We will critically assess the multilayered regulation of HAS 2, the most critical hyaluronan synthase, and its role in cancer growth, metabolism, and therapy.