Single-cell RNA sequencing has unveiled the contribution of ADSCs in reprogramming metabolism in triple-negative breast cancer

Abstract

Abstract Background: Mesenchymal stem cells (MSCs) constitute a significant element of the tumor microenvironment (TME), exerting dynamic influences on various tumors through mechanisms such as chemotaxis, interaction with immune cells. Therefore, MSCs have the ability to dynamically affect various types of tumors. The purpose of this study was to determine the impact of three common MSCs on tumors using single-cell analysis technology. Methods: We accessed single-cell sequencing date for mesenchymal stromal stem cells from adipose tissue (ADSCs), human bone marrow (BMSCs), and stem cells from human exfoliated deciduous teeth (SHED) from GEO database (GSE157863). We utilized R packages, including Seurat and Rtsne, for analyzing difference between ADSCs and other MSCs. Subsequently, ADSCs were injected into nude mice bearing mammary tumor cells, and PET-CT was conducted to compare metabolic absorption rates before and after injection. Additionally, bioinformatic analysis and Immunohistochemistry (IHC) were utilized to investigate the function and distribution of CCDC80. Results: Bioinformatic analysis revealed that ADSCs differed from BMSCs and SHED, suggesting a potential inhibition of tumor growth through alterations in glycine metabolism. In vivo experiments using a triple-negative breast cancer model demonstrated that the injection of ADSCs inhibited tumor growth. Furthermore, our findings implicated CCDC80 as a potentially pivotal gene influencing metabolism. Conclusion: The data derived from this study indicate that ADSCs possess unique capabilities to modulate metabolism and suppress tumor growth. Consequently, ADSCs may emerge as a promising cellular treatment option for triple-negative breast cancer, a subtype currently lacking effective therapeutic interventions.