Hyaluronan, CD44 and Emmprin: partners in cancer cell chemoresistance

Drug Resist Updat. 2008 Jun;11(3):110-21. doi: 10.1016/j.drup.2008.04.002. Epub 2008 May 19.


Hyaluronan not only is an important structural component of extracellular matrices but also interacts with cells during dynamic cell processes such as those occurring in cancer. Consequently, interactions of hyaluronan with tumor cells play important cooperative roles in various aspects of malignancy. Hyaluronan binds to several cell surface receptors, including CD44, thus leading to co-regulation of signaling pathways that are important in regulation of multidrug resistance to anticancer drugs, in particular anti-apoptotic pathways induced by activation of receptor tyrosine kinases. Emmprin, a cell surface glycoprotein of the Ig superfamily, stimulates hyaluronan production and downstream signaling consequences. Emmprin and CD44 also interact with various multidrug transporters of the ABC family and monocarboxylate transporters associated with resistance to cancer therapies. Moreover, hyaluronan-CD44 interactions are critical to these properties in the highly malignant, chemotherapy-resistant cancer stem-like cells. Perturbations of the hyaluronan-CD44 interaction at the plasma membrane by various antagonists result in attenuation of receptor tyrosine kinase and transporter activities and inhibition of tumor progression in vivo. These antagonists, especially small hyaluronan oligomers, may be useful in therapeutic strategies aimed at preventing tumor refractoriness or recurrence due to drug-resistant sub-populations within malignant cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / physiology
  • Basigin / physiology*
  • Cell Membrane / metabolism
  • Cell Survival / physiology
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Hyaluronan Receptors / physiology*
  • Hyaluronic Acid / physiology*
  • Monocarboxylic Acid Transporters / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Phenotype
  • Signal Transduction


  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Hyaluronan Receptors
  • Monocarboxylic Acid Transporters
  • Basigin
  • Hyaluronic Acid