G-protein coupled receptor 183 (GPR183) inhibits visceral metastasis of non-small cell lung cancer.

IF 3.2 3区 医学 Q2 ONCOLOGY
Lei Cheng, Shifang Li, Zhenwen Cui, Xuezhi Sun, Mengqi Gong, Yun Chen, Li Meng, Yiwei Liao
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Abstract

Brain metastasis is a serious complication of non-small cell lung cancer (NSCLC) that contributes to poor survival outcomes despite strides made in systemic treatment regimens. The G protein-coupled receptor GPR183 has been shown to regulate immune cell positioning; however, its role in lung cancer metastasis remains unclear. In this study, the specific effects of G-protein coupled receptor 183 (GPR183) on lung cancer cell phenotypes and a mouse brain and lung metastasis model were investigated in vitro and in vivo. Lung cancer cell lines with GPR183 overexpression were assessed for proliferation, apoptosis, and cell cycle progression through CCK-8, flow cytometry, and immunoblotting. Wound healing, Transwell migration, and invasion assays were used to investigate the metastatic potential of GPR183-overexpressing cells. Subcutaneous xenograft and lung metastasis models were used to examine the growth and metastasis ability of GPR183-overexpressing cells. Moreover, a brain metastasis model was established using A549 cells that were injected into mice, and tumor burden was monitored using bioluminescence imaging and IHC staining. The overexpression of GPR183 inhibited lung cancer cell proliferation, migration, and invasion by inhibiting ERK and Akt pathways. GPR183 also reduced angiogenesis in co-cultured endothelial cells and limited the invasion of lung cancer cells through the blood-brain barrier. In the mouse model, GPR183 significantly reduced metastatic burden. These findings suggest that GPR183 inhibits NSCLC visceral metastasis by modulating angiogenesis and metastatic pathways, presenting a potential therapeutic target for preventing brain metastasis in lung cancer patients.

g蛋白偶联受体183 (GPR183)抑制非小细胞肺癌内脏转移。
脑转移是非小细胞肺癌(NSCLC)的严重并发症,尽管在全身治疗方案方面取得了进展,但脑转移导致生存结果不佳。G蛋白偶联受体GPR183已被证明可调节免疫细胞定位;然而,其在肺癌转移中的作用尚不清楚。本研究在体外和体内研究了g蛋白偶联受体183 (GPR183)对肺癌细胞表型和小鼠脑肺转移模型的特异性影响。通过CCK-8、流式细胞术和免疫印迹技术评估GPR183过表达的肺癌细胞系的增殖、凋亡和细胞周期进展。伤口愈合、Transwell迁移和侵袭试验用于研究gpr183过表达细胞的转移潜力。采用皮下移植和肺转移模型检测过表达gpr183细胞的生长和转移能力。并将A549细胞注射小鼠,建立脑转移模型,采用生物发光成像和免疫组化染色监测肿瘤负荷。过表达GPR183通过抑制ERK和Akt通路抑制肺癌细胞的增殖、迁移和侵袭。GPR183还能减少共培养内皮细胞的血管生成,并限制肺癌细胞通过血脑屏障的侵袭。在小鼠模型中,GPR183显著降低转移负荷。这些发现表明GPR183通过调节血管生成和转移途径抑制NSCLC内脏转移,为预防肺癌患者脑转移提供了潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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