These observations form the basis of an important subject of investigation, regarding the effects of Gram-negative bacteria on cancer development. Further, postoperative pneumonias are a common complication of thoracic surgery and predominantly caused by Gram-negative bacteria ( 14- 16). Further studies pinpoint Gram-negative bacteria as the most frequent pathogen that led to increased mortality in NSCLC patients ( 12, 13). Pulmonary infections are very common and predict poor prognosis of NSCLC patients ( 11). Further studies on critical influential factors involved in outgrowth and metastasis of NSCLC cells, especially those focused on cancer cells from clinical patients, are urgently needed. Thus, current clinical therapeutic options for NSCLC patients are still limited and their prognoses remain far from acceptable ( 8- 10). However, patients who respond to targeted therapeutics first are frequently and quickly encountered with drug resistance. Recently, personalized treatment of NSCLC patients using targeted therapeutics, which are dominantly based on patients’ and tumors’ precise genetic defects, served as a promising direction for NSCLC clinical management ( 5- 7). In NSCLC patients, general outcomes of standard therapy including surgery, radiation therapy and chemotherapy are poor ( 3, 4). Non-small cell lung cancer (NSCLC) is the most common type and accounts for about 85% of all cases in patients with lung cancer ( 3). Lung cancer is the leading cause of cancer-related death worldwide, with an increasing incidence every year ( 1, 2). Keywords: Lung cancer Gram-negative bacteria lipid synthesis TLR4 TLR9 These findings reveal a new mechanism for pulmonary infection-trigged caner development and provide clues for exploring therapeutics for lung cancer patients. In lung cancer patients, higher expressions of innate immune receptors, TLR4 and TLR9, were observed in those with Gram-negative infections and associated with the aberrant lipid synthesis that was observed in vitro.Ĭonclusions: Pulmonary infections with Gram-negative bacteria lead to aberrant lipid synthesis through TLR4 and TLR9 signaling in lung cancer patients and result in rapid proliferation and metastasis of lung cancer cells. Interference with lipid synthesis efficiently abrogated Gram-negative-bacteria-induced lung cancer development. Knockdown of TLR4 and/or TLR9 was able to block Gram-negative bacteria mediated lipid synthesis and lung cancer development. Mechanistically, Gram-negative bacteria activate TLR4 and TLR9 signaling and enhance lipid synthesis in human lung cancer cells. Results: Gram-negative bacteria significantly promoted lung cancer development including growth and metastasis in dose dependent manner. Knockdown of TLR4 and TLR9 signaling was achieved by transfection with specific shRNAs and administration of specific antagonists. Block lipid synthesis was performed with C75 as a FAS inhibitor and transfection with ACC1 siRNA. Lipid synthesis was evidenced by expressions of FASN and ACC1, as well as BODIPY Fluorophores staining. Tumor growth and metastasis in vivo was evaluated in BALB/c nude mice. ![]() Tumor outgrowth and invasion in vitro was analyzed with MTT assay and Biocoat Matrigel Invasion Chamber. ![]() Methods: Lung cancer cells were isolated from clinical surgical tissues. Herein, we investigated the effect of the co-presence of Gram-negative bacteria on outgrowth and metastasis of lung cancer cells in clinical patients. Patients with lung cancer are very frequently present with pulmonary infections, in particular with Gram-negative bacteria. Interviews with Outstanding Guest Editorsīackground: Lung cancer is the leading cause of cancer-related death worldwide.Policy of Dealing with Allegations of Research Misconduct.Policy of Screening for Plagiarism Process.
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