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

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.