title: Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck.
abstract: Squamous cell carcinoma of the head and neck (HNSCC) metastasizes predictably to locoregional, cervical lymph nodes. Tumor cells can express various receptors that facilitate metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCRs), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. CCR expression was evaluated in HNSCC, and we showed a consistent pattern of CCR6 downregulation and upregulation of CCR7 in metastatic cells and tissues. Functional assays indicate that these surface receptors were functional on metastatic tumor cells. CCR6 downregulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, while CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly upregulated. 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 HNSCC cells in vivo. Our data indicate that inhibition of CCR signaling may provide a targeted molecular therapy to prevent HNSCC metastasis.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Hillman Cancer Center, Pittsburgh, PA 15213, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Tony E
authors.initials: TE
authors.lastname: Godfrey
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine