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

• DOI: 10.1038/onc.2013.75
• Publication Date: 2013-04-08T10:12:36Z
• Authors: 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
• Keywords: Mice, Knockout; 0301 basic medicine; Glycogen Synthase Kinase 3 beta; Lung Neoplasms; Smoking; Transcription Factor RelA; Pneumonia; Coculture Techniques; 3. Good health; Carcinoma, Lewis Lung; Glycogen Synthase Kinase 3; Mice; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Macrophages, Alveolar; Animals; Humans; Myeloid Cells; Transcriptome; Proto-Oncogene Proteins c-akt; Neoplasm Transplantation; Cell Proliferation

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.