title: Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070.
abstract: BACKGROUND
  Despite intensive research and novel adjuvant therapies, there is currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites such as the liver; however, the therapeutic blockade with the existing agents has proven difficult.
  
  
  METHODS
  AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the migration of melanoma cells compared with the commonly described antagonist AMD3100.
  
  
  RESULTS
  AMD11070 abrogated melanoma cell migration and was significantly more effective than AMD3100. Importantly for the clinical context, the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070.
  
  
  CONCLUSIONS
  Liver-resident myofibroblasts excrete CXCL12, which is able to promote the migration of CXCR4-expressing tumour cells from the blood into the liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic strategy for both B-RAF wild-type and mutated melanomas.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: G
authors.initials: G
authors.lastname: O'Boyle
authors.forename: I
authors.initials: I
authors.lastname: Swidenbank
authors.forename: H
authors.initials: H
authors.lastname: Marshall
authors.forename: C E
authors.initials: CE
authors.lastname: Barker
authors.forename: J
authors.initials: J
authors.lastname: Armstrong
authors.forename: S A
authors.initials: SA
authors.lastname: White
authors.forename: S P
authors.initials: SP
authors.lastname: Fricker
authors.forename: R
authors.initials: R
authors.lastname: Plummer
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: P E
authors.initials: PE
authors.lastname: Lovat
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002082:Butylamines; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors*; D005434:Flow Cytometry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D000634:Aminoquinolines; D001562:Benzimidazoles; D002082:Butylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D006573:Heterocyclic Compounds, 1-Ring; D019718:Receptors, CXCR4; C494414:mavorixafor
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