Surfactant Protein B Suppresses Lung Cancer Progression by Inhibiting Secretory Phospholipase A2 Activity and Arachidonic Acid Production

• Published in: Cellular physiology and biochemistry Vol. 42; no. 4; pp. 1684 - 1700
• Main Authors: Lee, Sungmin, Kim, Daehoon, Kang, JiHoon, Kim, EunGi, Kim, Wanyeon, Youn, HyeSook, Youn, BuHyun
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: A549 Cells; Animals; Arachidonic acid; Arachidonic Acid - antagonists & inhibitors; Arachidonic Acid - metabolism; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Culture Media, Conditioned - pharmacology; Disease Progression; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Gene expression; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Immunoglobulins; Kinases; Lipids; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; Male; Medical prognosis; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Neoplasm Transplantation; Original Paper; Penicillin; Phospholipase A2; Phospholipases A2, Secretory - antagonists & inhibitors; Phospholipases A2, Secretory - genetics; Phospholipases A2, Secretory - metabolism; Protein Kinase C-delta - genetics; Protein Kinase C-delta - metabolism; Proteins; Pulmonary Surfactant-Associated Protein B - genetics; Pulmonary Surfactant-Associated Protein B - metabolism; Radiation therapy; Radiation Tolerance - genetics; Radiation, Ionizing; Radioresistance; Respiratory distress syndrome; Signal Transduction; Surfactant protein B; Surfactants; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Grand Island; Surfactant protein B; Epithelial-mesenchymal transition; Radioresistance; Phospholipase A2; Arachidonic acid; Lung cancer
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000479418

Abstract Background/Aims: Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B). Methods: To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to evaluate the downstream signaling pathway. The in vivo effects of SP-B were assessed through mouse xenograft model with intratumoral injection of CM. Results: In response to IR, NSCLC cell lines showed decreased SP-B regulated by the TGF-β signaling and decreased SP-B stimulated cell survival and epithelial-mesenchymal transition. Treatment with CM from irradiated cells activated sPLA2, enhanced protein kinase Cδ-MAPKs signaling pathway, and increased arachidonic acid production. We confirmed the in vivo roles of SP-B through mouse xenograft model. Conclusion: Our results revealed that down-regulation of SP-B was involved in the radiation-induced metastatic conversion of NSCLC and provided evidence that SP-B acted as a suppressor of NSCLC progression.