Acute respiratory distress syndrome enhances tumor metastasis into lungs: Role of BRD4 in the tumor microenvironment

Acute respiratory distress syndrome (ARDS) is associated with severe lung inflammation, edema, hypoxia, and high vascular permeability. The COVID-19-associated pandemic ARDS caused by SARS-CoV-2 has created dire global conditions and has been highly contagious. Chronic inflammatory disease enhances cancer cell prolifer-ation, progression, and invasion. We investigated how acute lung inflammation activates the tumor microen-vironment and enhances lung metastasis in LPS induced in vitro and in vivo models. Respiratory illness is mainly caused by cytokine storm, which further influences oxidative and nitrosative stress. The LPS-induced inflam-matory cytokines made the conditions suitable for the tumor microenvironment in the lungs. In the present study, we observed that LPS induced the cytokine storm and promoted lung inflammation via BRD4, which further caused the nuclear translocation of p65 NF-Kappa B and STAT3. The transcriptional activation additionally triggers the tumor microenvironment and lung metastasis. Thus, BRD4-regulated p65 and STAT3 transcriptional activity in ARDS enhances lung tumor metastasis. Moreover, LPS-induced ARDS might promote the tumor microenvironment and increase cancer metastasis into the lungs. Collectively, BRD4 plays a vital role in inflammation-mediated tumor metastasis and is found to be a diagnostic and molecular target in inflammation-associated cancers.

Automated summary

Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 has led to global pandemics and is highly contagious. Inflammation, specifically cytokine storm, plays a critical role in promoting lung metastasis by creating suitable conditions for the tumor microenvironment. In this study, LPS-induced lung inflammation was found to activate BRD4, resulting in the nuclear translocation of p65 NF-Kappa B and STAT3, leading to transcriptional activation and enhanced tumor metastasis. Furthermore, LPS-induced ARDS may contribute to the promotion of the tumor microenvironment and increased lung metastasis. Collectively, BRD4 serves as a diagnostic and molecular target for inflammation-associated cancers.