Oncotarget

Research Papers:

CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases

Hina Mir, Rajesh Singh, Goetz H. Kloecker, James W. Lillard Jr. and Shailesh Singh _

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Oncotarget. 2015; 6:9985-9998. https://doi.org/10.18632/oncotarget.3194

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Abstract

Hina Mir1, Rajesh Singh1, Goetz H. Kloecker2, James W. Lillard Jr.1, Shailesh Singh1

1Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

2James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA

Correspondence to:

Shailesh Singh, e-mail: [email protected]

Keywords: CXCR6, CXCL16, lung cancer

Received: December 17, 2014     Accepted: January 23, 2015     Published: April 07, 2015

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.


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