title: CXCL12 and CXCR4, but not CXCR7, are primarily expressed by the stroma in head and neck squamous cell carcinoma.
abstract: The CXCL12/CXCR4 axis is involved in numerous models of metastatic dissemination, including head and neck squamous cell carcinoma (HNSCC). We assessed the relative expressions of CXCL12, CXCR4 and CXCR7 in the stroma and the tumour of HNSCC, and evaluated the methylation status of the CXCL12 promoter.Snap-frozen, HPV negative HNSCC samples were micro-dissected to isolate the tumoural and stromal compartments. The expression levels of CXCL12, CXCR4 and CXCR7 were assessed by qRT-PCR, and the methylation level of the CXCL12 promoter was evaluated by pyrosequencing.In total, 23 matched tumour/stroma samples were analysed. Higher expressions of CXCR4 and CXCL12 were observed in the stroma (p = 0.012 and p < 0.0001, respectively). No significant difference in expression was observed for CXCR7. A high methylation level (>40%) of the CXCL12 promoter was observed in only a few tumoural samples (5/23) and was associated with a lower expression of the gene (p = 0.03).Stromal cells, rather than the tumour itself, are mainly responsible for the expression of both CXCL12 and CXCR4 expression in HNSCC. CXCR7 expression did not differ between the two compartments and was not related to CXCL12 or CXCR4 expression. Finally, the methylation of the CXCL12 promoter could only explain the low intra-tumoural expression of this gene in 20% of cases.
authors.affiliation: 1Department of Medical Oncology, Centre Henri Becquerel, IRON, Rouen 2INSERM U918, Centre Henri Becquerel, IRIB, Rouen 3Department of Pathology, Centre Henri Becquerel, Rouen 4Department of Head and Neck Surgery, Hospital Charles Nicolle, Rouen 5Department of Head and Neck Surgery, Centre Henri Becquerel, Rouen 6Department of Pathology, Hospital Charles Nicolle, Rouen, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Clatot
authors.forename: Marie
authors.initials: M
authors.lastname: Cornic
authors.forename: Anca
authors.initials: A
authors.lastname: Berghian
authors.forename: Vinciane
authors.initials: V
authors.lastname: Marchand
authors.forename: Olivier
authors.initials: O
authors.lastname: Choussy
authors.forename: Faissal
authors.initials: F
authors.lastname: El Ouakif
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.forename: Sophie
authors.initials: S
authors.lastname: Laberge-Le-Couteulx
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Picquenot
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D054387:Receptors, CXCR / Q000032:analysis / Q000096:biosynthesis*; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: C501896:ACKR3 protein, human; D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4