Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells

D Li; C Beisswenger; C Herr; J Hellberg; G Han; T Zakharkina; M Voss; R Wiewrodt; R M Bohle; M D Menger; R M Schmid; D Stöckel; H-P Lenhof; R Bals

doi:10.1038/onc.2013.75

Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells

Oncogene. 2014 Mar 6;33(10):1239-48. doi: 10.1038/onc.2013.75. Epub 2013 Apr 8.

Authors

D Li¹, C Beisswenger¹, C Herr¹, J Hellberg¹, G Han¹, T Zakharkina¹, M Voss¹, R Wiewrodt², R M Bohle³, M D Menger⁴, R M Schmid⁵, D Stöckel⁶, H-P Lenhof⁶, R Bals¹

Affiliations

¹ Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
² Pulmonary Division, Department of Medicine A, Münster University Hospital, Münster, Germany.
³ Department of Pathology, Saarland University Hospital, Homburg, Germany.
⁴ Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany.
⁵ Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
⁶ Center for Bioinformatics, Saarland University, Saarbrücken, Germany.

PMID: 23563178
DOI: 10.1038/onc.2013.75

Abstract

Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease. The aim of this study was to investigate the role of myeloid cell nuclear factor-κB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 (rela(Δ-/-)) to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild-type mice. In CS-exposed rela(Δ-/-) mice, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt/β-catenin pathway. In conclusion, myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth and has a role in the activation of Wnt/β-catenin signaling in tumor cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Lewis Lung / etiology
Carcinoma, Lewis Lung / metabolism
Carcinoma, Lewis Lung / pathology
Carcinoma, Non-Small-Cell Lung / etiology
Carcinoma, Non-Small-Cell Lung / metabolism*
Carcinoma, Non-Small-Cell Lung / secondary
Cell Line, Tumor
Cell Proliferation*
Coculture Techniques
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Humans
Lung Neoplasms / etiology
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Macrophages, Alveolar / metabolism
Mice
Mice, Knockout
Myeloid Cells / metabolism*
Neoplasm Transplantation
Pneumonia / etiology
Pneumonia / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Smoking / adverse effects
Transcription Factor RelA / physiology*
Transcriptome
Tumor Burden
Tumor Necrosis Factor-alpha / metabolism
Wnt Signaling Pathway*
beta Catenin / metabolism

Substances

CTNNB1 protein, human
RELA protein, human
Transcription Factor RelA
Tumor Necrosis Factor-alpha
beta Catenin
Glycogen Synthase Kinase 3 beta
Proto-Oncogene Proteins c-akt
Glycogen Synthase Kinase 3