Mass spectrometry-based proteomics identifies Serpin B9 as a key protein in promoting bone metastases in lung cancer.
Yufeng HuangMing GongHongmin ChenChuangzhong DengXiaojun ZhuJiaming LinAnfei HuangYanyang XuYi TaiGuohui SongHuaiyuan XuJinxin HuHuixiong FengQinglian TangJinchang LuJin WangPublished in: Molecular cancer research : MCR (2024)
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 lung cancer patients, 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 (GrB), manifesting with the decreased infiltration of cytotoxic T cells (CTLs) and increased expression level of exhausted markers. A specific SB9-targeting inhibitor (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 LCBM patients. Implications: Serpin B9 as a therapeutic target for lung cancer bone metastasis.
Keyphrases
- poor prognosis
- mass spectrometry
- bone mineral density
- soft tissue
- bone loss
- squamous cell carcinoma
- bone regeneration
- mouse model
- small cell lung cancer
- long non coding rna
- postmenopausal women
- liquid chromatography
- cell proliferation
- high resolution
- induced apoptosis
- end stage renal disease
- body composition
- high performance liquid chromatography
- cell death
- transcription factor
- newly diagnosed
- climate change
- drug delivery
- binding protein
- capillary electrophoresis
- social media
- gas chromatography
- prognostic factors
- human health
- ms ms
- protein kinase