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Figure S7 from Mass Spectrometry–Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer

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posted on 2024-04-02, 07:21 authored by 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

Bone metastases of lung cancer patients’ demographic and clinical data

Funding

National Natural Science Foundation of China (NSFC)

National Natural Science Foundation of China-Guangdong Joint Fund (国家自然科学基金-广东省联合基金)

History

ARTICLE ABSTRACT

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. SB9 as a therapeutic target for LCBM.