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Home > Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function.

Wu, Shih-Ying and Xing, Fei and Sharma, Sambad and Wu, Kerui and Tyagi, Abhishek and Liu, Yin and Zhao, Dan and Deshpande, Ravindra Pramod and Shiozawa, Yusuke and Ahmed, Tamjeed and Zhang, Wei and Chan, Michael and Ruiz, Jimmy and Lycan, Thomas W and Dothard, Andrew and Watabe, Kounosuke . (2020) Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function. The Journal of Experimental Medicine, 217 (8 e20191131) doi: 10.1084/jem.20191131.

URL: https://rupress.org/jem/article/217/8/e20191131/15...

Up to 40% of lung cancer patients develop brain metastasis, and the median survival of these patients remains less than 6 months. Smoking is associated with lung cancer. However, how smoking impacts the development of brain metastasis remains elusive. We examined 281 lung cancer patients with distant metastasis and found that smokers exhibited a significantly high incidence of brain metastasis.

We found that nicotine enhanced brain metastasis, while a depletion of microglia suppressed this effect in vivo. Nicotine skewed the polarity of microglia to the M2 phenotype, thereby increasing the secretion of IGF-1 and CCL20, which promoted tumor progression and stemness. Importantly, nicotine enhanced the expression of SIRPα in microglia and restricted their phagocytic ability. We also identified a compound, parthenolide, that suppressed brain metastasis by blocking M2 polarization. Our results indicate that nicotine promotes brain metastasis by skewing the polarity of M2 microglia, which enhances metastatic tumor growth. Our results also highlight a potential risk of using nicotine for tobacco cessation.


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