Unraveling the metastatic niche in breast cancer bone metastasis through single‑cell RNA sequencing

• Xiangyu Li ^[2] ; Ziyu Gao ^[2] ; Meiling Yang ^[3] ; Ciqiu Yang ^[1] ; Dongyang Yang ^[1] ; Wenhui Cui ^[2] ; Dandan Wu ^[4] ; Jie Zhou ^[4]
  1. [1] Southern Medical University

     Southern Medical University

     China

     
  2. [2] The Stem Cell and Tissue Engineering Research Center, College of Pharmacy, Changzhi Medical College, Changzhi 046000, Shanxi, People’s Republic of China
  3. [3] Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
  4. [4] Department of Breast Oncology Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 27, Nº. 2, 2025, págs. 671-686
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. Through the study of the immune microenvironment in BRCA BoM offer perspectives for therapeutic interventions targeting this specific metastatic manifestation of BRCA.

    Methods This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primarytumors (PT), lymph node metastasis (LN), and BoM.

    Results and Conclusions Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancerassociated fibroblasts (CAFs) and reduced immune cell presence. A distinct subtype (State 1) of BRCA BoM cells associated with adverse prognosis is identified. State 1, displaying heightened stemness traits, may represent aninitiation phase for BoM in BRCA. Complex cell communications involving tumor, stromal, and immune cells are revealed. Interactions of FN1, SPP1, and MDK correlate with elevated immune cells in BoM. CD46, MDK, and PTNinteractions drive myofibroblast activation and proliferation, contributing to tissue remodeling. Additionally, MDK, PTN,and FN1 interactions influence FAP+ CAF activation, impacting cell adhesion and migration in BoM. These insightsdeepen our understanding of the metastatic niche in breast cancer BoM.