Single-cell sequencing analysis reveals the relationship between tumor microenvironment cells and oxidative stress in breast cancer bone metastases

Abstract

Bone metastasis (BM) is one of the main manifestations of advanced breast cancer (BC), causing complications such as pathological fractures, which seriously affects the quality of life of patients and even leads to death. In our study, a global single-cell landscape of the tumor microenvironment was constructed using single cell RNA sequencing data from BM. BC cells were found to be reduced in the BM, while mesenchymal stem cells (MSCs), Fibroblasts and other cells were significantly more abundant in the BM. The subpopulations of these cells were further identified, and the pathways, developmental trajectories and transcriptional regulation of different subpopulations were discussed. The results suggest that with the development of BM, BC cells were vulnerable to oxidative damage, showing a high level of oxidative stress, which played a key role in cell apoptosis. Fibroblasts were obviously involved in the biological processes (BPs) related to ossification and bone remodeling, and play an important role in tumor cell inoculation to bone marrow and growth. MSC subpopulations were significantly enriched in a number of BPs associated with bone growth and development and oxidative stress and may serve as key components of BC cells homing and adhesion to the ecological niche of BM. In conclusion, our research results describe the appearance of tumor microenvironment cell subpopulations in breast cancer patients, reveal the important role of some cells in the balance of BM bone remodeling and the imbalance of BM development, and provide potential therapeutic targets for BM.