Lymphotoxin-β promotes breast cancer bone metastasis colonization and osteolytic outgrowth.

Autor: Wang X; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Zhang T; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Zheng B; Department of Orthopedic Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China., Lu Y; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Liang Y; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Xu G; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Zhao L; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Tao Y; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Song Q; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., You H; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Hu H; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Li X; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Sun K; Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Li T; School of Life Sciences and Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, China., Zhang Z; Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Wang J; School of Life Sciences and Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, China., Lan X; State Key Laboratory of Molecular Oncology and Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Pan D; State Key Laboratory of Molecular Oncology and Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Fu YX; State Key Laboratory of Molecular Oncology and Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China., Yue B; Department of Orthopedic Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China. bonetumoryb@qdu.edu.cn., Zheng H; State Key Laboratory of Molecular Oncology and Center for Cancer Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China. hanzheng@tsinghua.edu.cn.; SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, Taiyuan, China. hanzheng@tsinghua.edu.cn.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Sep; Vol. 26 (9), pp. 1597-1612. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1038/s41556-024-01478-9
Abstrakt: Bone metastasis is a lethal consequence of breast cancer. Here we used single-cell transcriptomics to investigate the molecular mechanisms underlying bone metastasis colonization-the rate-limiting step in the metastatic cascade. We identified that lymphotoxin-β (LTβ) is highly expressed in tumour cells within the bone microenvironment and this expression is associated with poor bone metastasis-free survival. LTβ promotes tumour cell colonization and outgrowth in multiple breast cancer models. Mechanistically, tumour-derived LTβ activates osteoblasts through nuclear factor-κB2 signalling to secrete CCL2/5, which facilitates tumour cell adhesion to osteoblasts and accelerates osteoclastogenesis, leading to bone metastasis progression. Blocking LTβ signalling with a decoy receptor significantly suppressed bone metastasis in vivo, whereas clinical sample analysis revealed significantly higher LTβ expression in bone metastases than in primary tumours. Our findings highlight LTβ as a bone niche-induced factor that promotes tumour cell colonization and osteolytic outgrowth and underscore its potential as a therapeutic target for patients with bone metastatic disease.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: