Stem Cell Reviews and Reports

, Volume 12, Issue 4, pp 464–475 | Cite as

Role of Pericellular Matrix in the Regulation of Cancer Stemness

  • Sofia Avnet
  • Margherita Cortini


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.


Sarcoma Hyaluronan CD44 Cancer stem cell Pericellular matrix 


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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Orthopaedic Pathophysiology and Regenerative Medicine UnitIstituto Ortopedico Rizzoli (IOR)BolognaItaly
  2. 2.Department of Biomedical and Neuromotor SciencesUniversity of BolognaBolognaItaly

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