癌症研究
肺癌
转移
免疫疗法
免疫系统
骨转移
细胞毒性T细胞
癌症
舍宾
癌细胞
蛋白质组学
生物
医学
免疫学
病理
内科学
生物化学
基因
体外
作者
Yufeng Huang,Ming Gong,Hongmin Chen,Chuangzhong Deng,Xiaojun Zhu,Jiaming Lin,Anfei Huang,Yanyang Xu,Yi Tai,Guohui Song,Huaiyuan Xu,Jinxin Hu,Huixiong Feng,Qinglian Tang,Jinchang Lu,Jin Wang
标识
DOI:10.1158/1541-7786.mcr-23-0310
摘要
Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM.
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