Junliang Ma1, Shaolin Chen2, Yingjie Liu3, Hao Han4, Ming Gong4, Yongxiang Song4. 1. Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, People's Republic of China. majunliang2021@sina.com. 2. School of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, People's Republic of China. 3. Department of Cardiovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, People's Republic of China. 4. Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, People's Republic of China.
Abstract
BACKGROUND: It has been reported that tumor-associated macrophages (TAMs) participate in modulating the progression of cancer in the tumor microenvironment. However, the crosstalk between TAMs and non-small cell lung cancer (NSCLC) is still unclear. OBJECTIVE: We investigated whether NSCLC-derived exosomes could affect TAMs, which feedback modulated progression of NSCLC. METHODS: MiR-181b expression was measured by RT-PCR. Human THP-1 monocyte was differentiated into macrophages with phorbol myristate acetate, which were further identified by transmission electron microscopy and western blot. Macrophage M1 and M2 polarizations were detected by flow cytometry, RT-PCR and western blot. Proliferation, migration, and invasion of NSCLC cells treated with conditioned mediums were detected by EdU and Transwell assays. RESULTS: We demonstrated that miR-181b was up-regulated in exosomes derived from NSCLC patients' serum and NSCLC cells. MiR-181b could be transferred to macrophages via exosomes in the co-culture system of macrophages and NSCLC cells, which promoted macrophage M2 polarization. Further examinations revealed that exosomes derived from NSCLC cells could enhanced macrophage M2 polarizations by regulating miR-181b/JAK2/STAT3 axis, and silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could reverse the effects. Importantly, the conditioned medium of macrophages treated with NSCLC cell-derived exosomes could promote NSCLC cell proliferation, migration, and invasion. Silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could block the effects. CONCLUSIONS: All of these results indicated that exosomal miR-181b participated in the crosstalk between NSCLC cells and TAMs, providing potential therapeutic targets for NSCLC.
BACKGROUND: It has been reported that tumor-associated macrophages (TAMs) participate in modulating the progression of cancer in the tumor microenvironment. However, the crosstalk between TAMs and non-small cell lung cancer (NSCLC) is still unclear. OBJECTIVE: We investigated whether NSCLC-derived exosomes could affect TAMs, which feedback modulated progression of NSCLC. METHODS: MiR-181b expression was measured by RT-PCR. Human THP-1 monocyte was differentiated into macrophages with phorbol myristate acetate, which were further identified by transmission electron microscopy and western blot. Macrophage M1 and M2 polarizations were detected by flow cytometry, RT-PCR and western blot. Proliferation, migration, and invasion of NSCLC cells treated with conditioned mediums were detected by EdU and Transwell assays. RESULTS: We demonstrated that miR-181b was up-regulated in exosomes derived from NSCLC patients' serum and NSCLC cells. MiR-181b could be transferred to macrophages via exosomes in the co-culture system of macrophages and NSCLC cells, which promoted macrophage M2 polarization. Further examinations revealed that exosomes derived from NSCLC cells could enhanced macrophage M2 polarizations by regulating miR-181b/JAK2/STAT3 axis, and silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could reverse the effects. Importantly, the conditioned medium of macrophages treated with NSCLC cell-derived exosomes could promote NSCLC cell proliferation, migration, and invasion. Silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could block the effects. CONCLUSIONS: All of these results indicated that exosomal miR-181b participated in the crosstalk between NSCLC cells and TAMs, providing potential therapeutic targets for NSCLC.
Authors: Jason D Arroyo; John R Chevillet; Evan M Kroh; Ingrid K Ruf; Colin C Pritchard; Donald F Gibson; Patrick S Mitchell; Christopher F Bennett; Era L Pogosova-Agadjanyan; Derek L Stirewalt; Jonathan F Tait; Muneesh Tewari Journal: Proc Natl Acad Sci U S A Date: 2011-03-07 Impact factor: 11.205
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702