Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Nature. 2024 Aug;632(8024):429-436. doi: 10.1038/s41586-024-07698-1. Epub 2024 Jul 10.
Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN tip cells at the SI stage (APLN Tip) advanced to Tip cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN Tip cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1 matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.
肿瘤可以通过血液供应获得进展和转移所需的营养和氧气。诱导血管生成涉及已建立的血管床的发芽及其成熟为有组织的网络。在这里，我们以单细胞分辨率生成了肿瘤脉管系统的综合图谱，涵盖了来自 31 种癌症类型的 372 位供体的大约 200,000 个细胞。轨迹推断表明，肿瘤血管生成是从静脉内皮细胞开始的，并向动脉内皮细胞延伸。随着新血管的延长（通过血管生成阶段 SI、SII 和 SIII），SI 阶段的 APLN 尖端细胞（APLN Tip）向 Notch 信号增加的尖端细胞推进。同时，紧跟在尖端细胞后面的柄细胞从高趋化因子表达过渡到 TEK（也称为 Tie2）表达增加。此外，APLN Tip 细胞不仅与疾病进展和预后不良有关，而且有望预测对抗 VEGF 治疗的反应。淋巴管内皮细胞表现出两种不同的分化谱系：一种负责淋巴管生成，另一种参与抗原呈递。在内皮细胞周围细胞中，内质网应激与产生 BASP1 基质的促血管生成周细胞有关。此外，细胞间通讯分析表明，新血管内皮细胞可以塑造有利于血管生成的免疫抑制微环境。这项研究描绘了肿瘤血管系统的复杂性，对抗血管生成治疗具有潜在的临床意义。
