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Chemotaxis towards hyaluronan is dependent on CD44 expression and modulated by cell type variation in CD44-hyaluronan binding.

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Date
2005-11
ICR Author
Isacke, Clare
Author
Tzircotis, G
Thorne, RF
Isacke, CM
Type
Journal Article
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Abstract
The accumulation of the extracellular matrix glycosaminoglycan hyaluronan by tumours and tumour-associated stroma promotes cancer cell invasion and metastasis. Using the Dunn chamber chemotaxis assay, we demonstrate for the first time that high molecular mass hyaluronan acts as a soluble chemoattractant promoting the directional migration of MDA-MB-468 and MDA-MB-231 breast cancer cells. Moreover, chemotaxis towards hyaluronan, but not foetal bovine serum, can be abrogated following treatment of the cells with siRNA oligonucleotides to downregulate CD44 expression. These data indicate that CD44 is the principal receptor mediating this response and that CD44 expression is not a general requirement for cell migration and gradient sensing, rather it elicits a ligand-specific response. However, expression of CD44 alone is not sufficient to drive chemotaxis towards hyaluronan, as NIH-3T3 fibroblasts were unable to respond to a hyaluronan gradient even when transfected with high levels of human CD44. For NIH-3T3 cells to bind exogenous hyaluronan, it was necessary to both increase the level of receptor expression and remove a hyaluronan pericellular matrix. Together, these studies reveal a direct mechanism for promoting cell invasion into the hyaluronan-rich matrix and predict that in the complex multicellular environment in vivo, multiple mechanisms exist to regulate the ability of a cell to respond to a chemotactic hyaluronan gradient.
URI
https://repository.icr.ac.uk/handle/internal/2236
DOI
https://doi.org/10.1242/jcs.02629
Collections
  • Breast Cancer Research
Subject
Cell Line, Tumor
NIH 3T3 Cells
Membrane Microdomains
Fibroblasts
Animals
Humans
Mice
Breast Neoplasms
Hyaluronic Acid
Detergents
Microscopy, Confocal
Transfection
Chemotaxis, Leukocyte
Protein Binding
Molecular Weight
Solubility
Hyaluronan Receptors
Research team
Molecular Cell Biology
Language
eng
License start date
2005-11
Citation
Journal of cell science, 2005, 118 (Pt 21), pp. 5119 - 5128

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