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dc.contributor.authorTzircotis, G
dc.contributor.authorThorne, RF
dc.contributor.authorIsacke, CM
dc.date.accessioned2018-07-31T14:28:23Z
dc.date.issued2005-11
dc.identifier.citationJournal of cell science, 2005, 118 (Pt 21), pp. 5119 - 5128
dc.identifier.issn0021-9533
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2236
dc.identifier.eissn1477-9137
dc.identifier.doi10.1242/jcs.02629
dc.description.abstractThe 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.
dc.formatPrint-Electronic
dc.format.extent5119 - 5128
dc.languageeng
dc.language.isoeng
dc.subjectCell Line, Tumor
dc.subjectNIH 3T3 Cells
dc.subjectMembrane Microdomains
dc.subjectFibroblasts
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectBreast Neoplasms
dc.subjectHyaluronic Acid
dc.subjectDetergents
dc.subjectMicroscopy, Confocal
dc.subjectTransfection
dc.subjectChemotaxis, Leukocyte
dc.subjectProtein Binding
dc.subjectMolecular Weight
dc.subjectSolubility
dc.subjectHyaluronan Receptors
dc.titleChemotaxis towards hyaluronan is dependent on CD44 expression and modulated by cell type variation in CD44-hyaluronan binding.
dc.typeJournal Article
rioxxterms.versionofrecord10.1242/jcs.02629
rioxxterms.licenseref.startdate2005-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of cell science
pubs.issuePt 21
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.publication-statusPublished
pubs.volume118
pubs.embargo.termsNot known
icr.researchteamMolecular Cell Biologyen_US
dc.contributor.icrauthorIsacke, Clareen


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