Single-cell RNA-Seq analysis reveals the tumorigenic microenvironment of interface zone of human breast cancer

The interface zone around invasive carcinoma can be thought of the actual tissue of tumor microenvironment with precedent alterations for tumor invasion. To characterize interface zones, we divided human breast carcinoma tissue into tumor zones, normal zones, and interface zones with 5-mm wide belts between the tumor invasion front and the normal zone and profiled total 88548 high quality cells from all three zones using single-cell RNA-sequencing. Through data analysis, validation and functional experiments, we revealed that interface zones possess specific phenotype molding of stromal cells. Especially, we found a specific gene BMPR1B whose expression in luminal cells gradually increased from normal zone to interface zone to tumor zone had abilities to promote proliferation, migration, clonal formation, and tumorigenicity of breast cancer cells. Our work allows for deeper insights into tumor microenvironment of breast cancer that will be served as a helpful resource for advancing breast cancer diagnosis and therapy.