Tumor‐associated macrophages promote the metastasis and growth of non‐small‐cell lung cancer cells through NF‐κB/PP2Ac‐positive feedback loop
| العنوان: | Tumor‐associated macrophages promote the metastasis and growth of non‐small‐cell lung cancer cells through NF‐κB/PP2Ac‐positive feedback loop |
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| المؤلفون: | Kai Chen, Meng-Yao Wu, Zhan-Wen Liang, Wei-Ming Duan, Songbing Qin, Meng Shen, Hualong Qin, Wei Li, Xin-Xin Ge, Yan Zhang, Xiao-Meng Liu, Meng-Dan Xu |
| المصدر: | Cancer Science |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Lung Neoplasms, tumor‐associated macrophages, Carcinogenesis, Angiogenesis, Chemokine CXCL1, non-small cell lung cancer (NSCLC), IκB kinase, Metastasis, Mice, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Tumor-Associated Macrophages, Protein Phosphatase 2, non‐small‐cell lung cancer, Feedback, Physiological, education.field_of_study, Neovascularization, Pathologic, Chemistry, NF-kappa B, General Medicine, Middle Aged, CXCL1, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Disease Progression, Original Article, medicine.symptom, Signal Transduction, Population, COL6A1, Inflammation, Collagen Type VI, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, education, Lung cancer, Cell Proliferation, protein phosphatase 2A, Original Articles, medicine.disease, Disease Models, Animal, 030104 developmental biology, Cancer research |
| الوصف: | Non‐small‐cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor‐associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor‐associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage‐conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF‐κB pathway‐dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF‐κB pathway signaling. Overexpression of PP2Ac, or the dominant‐negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF‐κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration. Tumor‐associated macrophages, the prominent type of inflammatory cells in non‐small‐cell lung cancer, can promote the growth and metastasis of cancer cells. Overexpression of PP2Ac, or the dominant‐negative forms of IKK or IκB, attenuated the acceleration on cancer cell growth and metastasis by TAMs. CXCL1 and COL6A1 could be downstream of NF‐κB/PP2Ac pathway. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted cancer cell proliferation and migration. |
| تدمد: | 1349-7006 1347-9032 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cc3270f7a7dd620e2c17ddd38611656 https://doi.org/10.1111/cas.14863 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0cc3270f7a7dd620e2c17ddd38611656 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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