Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype.
Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. Chemokine receptor expression was evaluated in SCCHN, using paired primary and metastatic tumors cell lines, and paired primary and metastatic biopsies from the same patients. Quantitative reverse transcription-PCR showed a consistent pattern of CCR6 down-regulation and up-regulation of CCR7 in metastatic cells and tissues. Chemotaxis assays, ligand-induced receptor down-regulation, and specific antibody blocking experiments supported the quantitative reverse transcription-PCR results, indicating that these surface receptors were functional on metastatic tumor cells. Cells derived from a highly metastatic mouse model of SCCHN were used to confirm CCR7 up-regulation in tumor cells with higher metastatic potential. CCR6 down-regulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, whereas CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly up-regulated. Thus, CCR6, CCR7, and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of SCCHN cells in vivo.
Department of Otolaryngology and Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
Jun
J
Wang
Liqiang
L
Xi
Jennifer L
JL
Hunt
William
W
Gooding
Theresa L
TL
Whiteside
Zhuo
Z
Chen
Tony E
TE
Godfrey
Robert L
RL
Ferris
D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D045744:Cell Line, Tumor; D002633:Chemotaxis; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C106311:CCR6 protein, human; C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine