title: Role of Pericellular Matrix in the Regulation of Cancer Stemness.
abstract: Cancer stem cells (CSC) are a prominent component of the tumor bulk and extensive research has now identified them as the subpopulation responsible for tumor relapse and resistance to anti-cancer treatments. Surrounding the bulk formed of tumor cells, an extracellular matrix contributes to cancer growth; the main component of the tumor micro-environment is hyaluronan, a large disaccharide forming a molecular network surrounding the cells. The hyaluronan-dependent coat can regulate cell division and motility in cancer progression and metastasis. One of the receptors of hyaluronan is CD44, a surface protein frequently used as a CSC marker. Indeed, tumor cells with high levels of CD44 appear to exhibit CSC properties and are characterized by elevated relapse rate. The CD44-hyaluronan-dependent interactions are Janus-faced: on one side, they have been shown to be crucial in both malignancy and resistance to therapy; on the other, they represent a potential value for future therapies, as disturbing the CD44-hyaluronan axis would not only impair the pericellular matrix but also the subpopulation of self-renewing oncogenic cells. Here, we will review the key roles of HA and CD44 in CSC maintenance and propagation and will show that CSC-like spheroids from a rabdhomyosarcoma cell line, namely RD, have a prominent pericellular coat necessary for sphere formation and for elevated migration. Thus, a better understanding of the hyaluronan-CD44 interactions holds the potential for ameliorating current cancer therapies and eradicating CSC.
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136, Bologna, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), 40136, Bologna, Italy. margherita.cortini@ior.it.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. margherita.cortini@ior.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Cortini
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid
keywords: CD44; Cancer stem cell; Hyaluronan; Pericellular matrix; Sarcoma