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Role of Pericellular Matrix in the Regulation of Cancer Stemness

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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.

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Funding and acknowledgments

This study was supported by Associazione Italiana Ricerca sul Cancro (AIRC to NB, no: 15608), by Ministry of Instruction and Education (FIRB to NB, no RBAP10447J), 5xMille 2012 to NB and PRrU Oncologia “Programma di ricerca Regione-Università 2010-2012” to NB.

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Avnet, S., Cortini, M. Role of Pericellular Matrix in the Regulation of Cancer Stemness. Stem Cell Rev and Rep 12, 464–475 (2016). https://doi.org/10.1007/s12015-016-9660-x

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