Unraveling the Metastatic Niche in Breast Cancer Bone Metastasis through Single-Cell RNA Sequencing

Abstract Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primary tumors (PT), lymph node metastasis (LN), and BoM. 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.