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Hyaluronan binding by cell surface CD44.

J Lesley1, V C Hascall, M Tammi

  • 1Cancer Biology Laboratory, The Salk Institute, San Diego, California 92186-5800, USA. lesley@salk.edu

The Journal of Biological Chemistry
|June 29, 2000
PubMed
Summary
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Hyaluronan (HA) binding to CD44 receptors is complex, influenced by HA size and CD44 activation. Monoclonal antibody treatment dramatically increases HA binding avidity to CD44.

Area of Science:

  • Cell biology
  • Biochemistry
  • Biophysics

Background:

  • CD44 is the principal cell surface receptor for hyaluronan (HA), a major component of the extracellular matrix.
  • HA-CD44 interactions are crucial for various cellular processes, including cell adhesion, migration, and proliferation.

Purpose of the Study:

  • To investigate the factors influencing the avidity of hyaluronan binding to cell surface CD44.
  • To determine the impact of hyaluronan size and CD44 activation state on binding affinity.

Main Methods:

  • Utilized fluorescein-conjugated hyaluronan to measure binding to various cell types.
  • Employed unlabeled hyaluronan preparations of defined sizes to assess competitive binding.
  • Investigated the effect of CD44-specific monoclonal antibody (mAb) treatment on hyaluronan binding avidity and kinetics.

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Main Results:

  • Hyaluronan binding avidity is a multivalent event influenced by hyaluronan size, CD44 quantity/density, and CD44 activation state.
  • Monovalent binding was observed for hyaluronan oligomers of 6-18 sugars.
  • Avidity increased significantly (approximately 3-fold) for oligomers of 20-38 sugars, indicating divalent binding.
  • Treatment with an inducing mAb (IRAWB14) dramatically enhanced avidity with increasing oligomer size, with minimal impact on binding kinetics but significantly delayed dissociation.

Conclusions:

  • CD44-mediated hyaluronan binding is size-dependent and significantly modulated by receptor activation.
  • Inducing mAb treatment potentiates CD44 avidity for hyaluronan, primarily by reducing ligand dissociation rate.
  • These findings provide insights into the complex regulation of cell-matrix interactions involving CD44 and hyaluronan.