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CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway

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Abstract

Absent in melanoma 2 (AIM2) has been reported to be an important inflammasome component that exerts tumor suppression in several tumors. However, whether CCL19/CCR7/AIM2 is involved in the progression of GC still remains unclear. Quantitative real-time and ELISA assay were used to determine the expressions of AIM2, CCL19 and CCR7 in GC tissues and cell lines. CCK-8, Edu staining, flow cytometry, Transwell assay, and tumorigenesis in nude mice were used to explore the function of AIM2 and CCL19 in vitro and in vivo. Apoptosis and inflammation-related biomarkers were detected by Western blot and ELISA assay. H&E staining was used to assess the histological changes in the subcutaneous tumor model. Immunohistochemistry (IHC) was used to evaluate the expression of Ki-67. We found that expression levels of AIM2, CCL19 and CCR7 were obviously lower in early GC tissues than those in progressive GC tissues. In vitro assays revealed that CCL19 treatment could enhance the suppressive effects of AIM2 overexpression on cell proliferation, migration, and invasion through CCR7. An in vivo assay also demonstrated that silencing of AIM2 reversed the suppressive effects of CCL19 on tumor growth. Collectively, CCL19 overexpression significantly inhibited GC cell proliferation and tumor growth in vitro and in vivo by up-regulating the CCR7/AIM2 pathway. Thus, CCL19 activated CCR7/AIM2 signaling pathway and it may be a potential therapeutic approach for GC therapy.

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Acknowledgement

Thanks to Dr. Edward C. Mignot, Shandong University, for linguistic advice.

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Authors and Affiliations

  1. Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, 430060, Hubei, People’s Republic of China

    Rui Zhou, Jun Sun, Chunping He, Chao Huang & Honggang Yu

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  1. Rui Zhou
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  2. Jun Sun
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  3. Chunping He
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  4. Chao Huang
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  5. Honggang Yu
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Contributions

RZ and HGY designed the experiments. RZ performed the experiments and collected the data with JS. JS and CPH organized and analyzed the data. CH and HGY validated the data analysis. RZ completed the draft of manuscript. CH and HGY revised the manuscript. Manuscript was been reviewed by all authors before submission.

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Correspondence to Honggang Yu.

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All authors declared no potential conflict of interest.

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The study was performed in accordance with the Declaration of Helsinki and obtained the approval from the Ethics Committee of the Renmin Hospital of Wuhan University.

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Zhou, R., Sun, J., He, C. et al. CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway. Human Cell 33, 1120–1132 (2020). https://doi.org/10.1007/s13577-020-00375-1

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  • DOI: https://doi.org/10.1007/s13577-020-00375-1

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