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Lymphotoxin-ß promotes breast cancer bone metastasis colonization and osteolytic outgrowth.
Wang, Xuxiang; Zhang, Tengjiang; Zheng, Bingxin; Lu, Youxue; Liang, Yong; Xu, Guoyuan; Zhao, Luyang; Tao, Yuwei; Song, Qianhui; You, Huiwen; Hu, Haitian; Li, Xuan; Sun, Keyong; Li, Tianqi; Zhang, Zian; Wang, Jianbin; Lan, Xun; Pan, Deng; Fu, Yang-Xin; Yue, Bin; Zheng, Hanqiu.
Afiliación
  • 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.
Nat Cell Biol ; 26(9): 1597-1612, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39147874
ABSTRACT
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-ß (LTß) is highly expressed in tumour cells within the bone microenvironment and this expression is associated with poor bone metastasis-free survival. LTß promotes tumour cell colonization and outgrowth in multiple breast cancer models. Mechanistically, tumour-derived LTß 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 LTß signalling with a decoy receptor significantly suppressed bone metastasis in vivo, whereas clinical sample analysis revealed significantly higher LTß expression in bone metastases than in primary tumours. Our findings highlight LTß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteólisis / Neoplasias Óseas / Neoplasias de la Mama / Linfotoxina beta Límite: Animals / Female / Humans Idioma: En Revista: Nat Cell Biol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteólisis / Neoplasias Óseas / Neoplasias de la Mama / Linfotoxina beta Límite: Animals / Female / Humans Idioma: En Revista: Nat Cell Biol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido