CCR9/CCL25 expression in non-small cell lung cancer correlates with aggressive disease and mediates key steps of metastasis
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Pranav Gupta1, Praveen K. Sharma2, Hina Mir1, Rajesh Singh1, Nalinaksha Singh1, Goetz H. Kloecker3, James W. Lillard Jr1 and Shailesh Singh1
1 Morehouse School of Medicine, Atlanta, GA, USA
2 School of Natural Sciences, Center of Life Sciences, Central University of Jharkhand, Ranchi, India
3 James Graham Brown Cancer Center, University of Louisville, School of Medicine, Louisville, KY, USA
Shailesh Singh, email:
Keywords: CCR9, CCL25, Chemokine receptor, Non-small cell lung cancer
Received: August 05, 2014 Accepted: September 24, 2014 Published: September 25, 2014
Poor clinical outcome of lung cancer (LuCa) is primarily due to lack of knowledge about specific molecules involved in its progression and metastasis. In this study, we for the first time show the clinical and biological significance of CC chemokine receptor-9 (CCR9) in non-small cell lung cancer (NSCLC). Expression of CCR9 and CCL25, the only natural ligand of CCR9, was significantly higher (p < 0.0001) in NSCLC tissues and serum respectively, compared to their respective controls. Interestingly, expression of both CCR9 and CCL25 was significantly higher in adenocarcinomas (ACs) compared to squamous cell carcinomas (SCCs) (p = 0.04, and p < 0.0001). Similar to tissues, AC and SCC cell lines were positive for CCR9 expression. Despite of marginal difference in CCR9 expression, AC cells showed higher migratory and invasive potential in response to CCL25, compared to SCC cells. This differential biological response of AC cells was primarily due to differential expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases under the influence of CCL25. Our results suggest CCR9 as a potential target for developing new treatment modality for NSCLC. Additionally, differential serum CCL25 level in ACs and SCCs, two NSCLC subtypes, suggest its potential as a non-invasive diagnostic/prognostic biomarker.
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