title: CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases.
abstract: Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target.
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Hina
authors.initials: H
authors.lastname: Mir
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
authors.affiliation: James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Goetz H
authors.initials: GH
authors.lastname: Kloecker
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Lillard
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Singh
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism*; D009362:Neoplasm Metastasis; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D051116:Receptors, Scavenger / Q000378:metabolism; D011991:Receptors, Virus / Q000096:biosynthesis*
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D053829:Amyloid Precursor Protein Secretases; D045726:Metalloproteases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: CXCL16; CXCR6; lung cancer