CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway
- PDF / 15,174,752 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 62 Downloads / 231 Views
RESEARCH ARTICLE
CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway Rui Zhou1 · Jun Sun1 · Chunping He1 · Chao Huang1 · Honggang Yu1 Received: 2 October 2019 / Accepted: 12 May 2020 © Japan Human Cell Society 2020
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. Keywords Gastric cancer · AIM2 · CCL19/CCR7 · Inflammation · Tumor growth
Introduction Gastric cancer (GC) is the second most common cause of tumor-related death worldwide [1]. Surgical resection plus adjuvant chemotherapy or radiotherapy have been the optimal approaches for GC therapy [2, 3], but it is still difficult to obtain satisfactory 5-year overall survival rates for most patients diagnosed in an advanced progressive stage [4]. Therefore, improving the early diagnosis at the molecular level in order to recognize and kill early GC cells is crucial for GC treatment. As a group of small chemotactic cytokines, chemokines can bind to seven-transmembrane G-protein-coupled receptors that activate downstream functions [5]. Chemokines and their receptors are induced by inflammatory cytokines, * Honggang Yu [email protected] 1
Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan 430060, Hubei, People’s Republic of China
growth factors, and other external stimuli in numerous cell types, including cancer cells [6, 7]. It is widely accepted that chemokines and their receptors are involved in important physiological processes, including organ development, angiogenesis, and host immune responses [8]. Recent studies have shown that chemokines and
Data Loading...
