title: CCR9/CCL25 expression in non-small cell lung cancer correlates with aggressive disease and mediates key steps of metastasis.
abstract: 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.
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Pranav
authors.initials: P
authors.lastname: Gupta
authors.affiliation: School of Natural Sciences, Center of Life Sciences, Central University of Jharkhand, Ranchi, India.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Sharma
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Hina
authors.initials: H
authors.lastname: Mir
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Nalinaksha
authors.initials: N
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: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Lillard
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Singh
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000097:blood; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D011379:Prognosis; D054388:Receptors, CCR / Q000096:biosynthesis* / Q000097:blood
chemical_list: C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D054388:Receptors, CCR