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. 2025 Feb;27(2):671-686.
doi: 10.1007/s12094-024-03594-2. Epub 2024 Jul 27.

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

Xiangyu Li #  1 , Ziyu Gao #  2 , Meiling Yang  3   4 , Ciqiu Yang  5 , Dongyang Yang  5 , Wenhui Cui  2 , Dandan Wu  6 , Jie Zhou  7
Affiliations

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

Xiangyu Li et al. Clin Transl Oncol. 2025 Feb.

Abstract

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 primary tumors (PT), lymph node metastasis (LN), and BoM.

Results and conclusions: Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancer-associated 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 an initiation 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 PTN interactions 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 insights deepen our understanding of the metastatic niche in breast cancer BoM.

Keywords: Bone metastasis; Breast cancer; Immune microenvironment; Myofibroblast-immune interactions; Single-cell RNA sequencing.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no conflict of interest. Ethical approval: This study was conducted in accordance with the Medical Ethics Committee of the Affiliated Cancer Hospital & Institute of Guangzhou Medical University. Informed consent: All participants provided informed consent prior to their participation.

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