乳腺癌是全球影响女性最常见的癌症。肿瘤内皮细胞（TECs）和恶性细胞是肿瘤微环境（TME）的主要组成部分，但它们的起源和在疾病起始、进展和治疗反应中的作用仍不清楚，因为存在显著的异质性。我们收集了来自8名乳腺癌患者的组织样本，采用单细胞RNA测序（scRNA-Seq）分析来研究肿瘤微环境中不同细胞亚群的存在情况。我们使用InferCNV来鉴定癌细胞。伪时轨迹分析揭示了乳腺癌血管生成的动态过程。我们在体外实验证实了小型胞外囊泡（sEVs）-源性蛋白磷酸酶1调节抑制因子亚基1B（PPP1R1B）的功能。我们对与乳腺癌血管生成相关的因素进行了单细胞转录组学分析，并确定了肿瘤微环境中涉及的12个内皮细胞亚群。我们还发现了TECs在肿瘤血管生成中的作用，并证实它们参与了血管生成的不同阶段，包括通过sEVs与其他细胞类型的相互通信。总体而言，该研究揭示了TECs的异质性和在不同阶段的肿瘤血管生成中的基因表达水平。本研究显示，乳腺癌恶性细胞来源的sEVs通过转移PPP1R1B激活内皮细胞，促进血管的形成，为人类乳腺癌抗血管生成治疗的开发提供了新的方向。© 2023. BioMed Central Ltd., part of Springer Nature.

Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity.Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments.We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis.This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer.© 2023. BioMed Central Ltd., part of Springer Nature.