Cheng Lei, Li Shifang, Cui Zhenwen, Sun Xuezhi, Gong Mengqi, Chen Yun, Meng Li, Liao Yiwei
Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
Department of Neurosurgery, Yiyang Central Hospital, Yiyang, 413099, Hunan, China.
Clin Exp Metastasis. 2025 Aug 4;42(5):44. doi: 10.1007/s10585-025-10360-3.
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.
脑转移是非小细胞肺癌（NSCLC）的一种严重并发症，尽管全身治疗方案取得了进展，但仍会导致不良的生存结果。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仍不清楚。在本研究中，在体外和体内研究了G蛋白偶联受体183（GPR183）对肺癌细胞表型以及小鼠脑和肺转移模型的具体影响。通过CCK-8、流式细胞术和免疫印迹评估过表达GPR183的肺癌细胞系的增殖、凋亡和细胞周期进程。采用伤口愈合、Transwell迁移和侵袭试验研究过表达GPR183的细胞的转移潜能。皮下异种移植和肺转移模型用于检测过表达GPR183的细胞的生长和转移能力。此外，使用注射到小鼠体内的A549细胞建立脑转移模型，并使用生物发光成像和免疫组化染色监测肿瘤负荷。GPR183的过表达通过抑制ERK和Akt途径抑制肺癌细胞的增殖、迁移和侵袭。GPR183还减少了共培养内皮细胞中的血管生成，并限制了肺癌细胞通过血脑屏障的侵袭。在小鼠模型中，GPR183显著降低了转移负担。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，为预防肺癌患者的脑转移提供了一个潜在的治疗靶点。
