2. Academic Validation
  3. Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer

Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer

  • Mol Cancer Res. 2024 Apr 2;22(4):402-414. doi: 10.1158/1541-7786.MCR-23-0310.
Yufeng Huang # 1 2 3,  Ming Gong # 1 2 3,  Hongmin Chen 1 2 3,  Chuangzhong Deng 1 2 3,  Xiaojun Zhu 1 2 3,  Jiaming Lin 1 2 3,  Anfei Huang 1 2 3,  Yanyang Xu 1 2 3,  Yi Tai 1 2 3,  Guohui Song 1 2 3,  Huaiyuan Xu 1 2 3,  Jinxin Hu 1 2 3,  Huixiong Feng 1 2,  Qinglian Tang 1 2 3,  Jinchang Lu 1 2 3,  Jin Wang 1 2 3
Affiliations

Affiliations

  • 1 Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
  • 2 State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
  • 3 Guangdong Provincial Clinical Research Center for Cancer, Guangdong, P.R. China.
  • # Contributed equally.
PMID: 38226993 DOI: 10.1158/1541-7786.MCR-23-0310
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.

Implications: SB9 as a therapeutic target for LCBM.

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