title: CXCR2 expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma.
abstract: CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small-molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis, and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma.
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Saintigny
authors.forename: Erminia
authors.initials: E
authors.lastname: Massarelli
authors.forename: Steven
authors.initials: S
authors.lastname: Lin
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Ahn
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Goswami
authors.forename: Baruch
authors.initials: B
authors.lastname: Erez
authors.forename: Michael S
authors.initials: MS
authors.lastname: O'Reilly
authors.forename: Diane
authors.initials: D
authors.lastname: Liu
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ping
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Solis Soto
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kim
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
authors.forename: Ja Seok
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D012907:Smoking
chemical_list: D023063:Receptors, Interleukin-8B