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Mechanical stretch promotes tumoricidal M1 polarization via the FAK/NF‐κB signaling pathway
Author(s) -
Shan Shengzhou,
Fang Bin,
Zhang Yifan,
Wang Chuandong,
Zhou Jia,
Niu Chenguang,
Gao Ya,
Zhao Danyang,
He Jiahao,
Wang Jing,
Zhang Xiaoling,
Li Qingfeng
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900799rr
Subject(s) - apoptosis , focal adhesion , cancer research , in vitro , chemistry , tumor microenvironment , melanoma , immunotherapy , nf κb , signal transduction , cytokine , cell growth , microbiology and biotechnology , immunology , medicine , biology , tumor cells , immune system , biochemistry
Macrophages (Mφs) can be used as a part of cell‐based cancer immunotherapy. However, they may be hampered by a failure to effectively and stably regulate their polarization state to enhance their tumoricidal effects. In this work, mechanical stretch (MS), as a biology‐free modulatory method, was shown to enhance M1 polarization and tumoricidal effects. By using an in vitro Flexcell Tension system, we found that murine Mφ RAW264.7 cells showed higher M1 polarization‐related mRNA expression and cytokine release after MS. Further molecular analyses found that focal adhesion kinase and NF‐κB activation occurred in the MS‐induced M1 polarization. Coculture of MS‐preconditioned Mφ with B16F10 skin melanoma cells in vitro showed that the proliferation of B16F10 cells decreased, whereas caspase‐3‐induced apoptosis increased. Importantly, the injection of MS‐preconditioned Mφ into murine skin melanomas in vivo impeded tumor growth; lesions were characterized by increased amounts of M1 Mφ, decreased tumor cell proliferation, and increased tumor cell apoptosis in the tumor microenvironment. Together, our results suggest that MS could be used as a simple preconditioning approach to prepare tumoricidal M1 Mφ for cancer immunotherapy.—Shan, S., Fang, B., Zhang, Y., Wang, C., Zhou, J., Niu, C., Gao, Y., Zhao, D., He, J., Wang, J., Zhang, X., Li, Q. Mechanical stretch promotes tumoricidal M1 polarization via the FAK/NF‐κB signaling pathway. FASEB J. 33, 13254–13266 (2019). www.fasebj.org