文章：

肿瘤血管生成的微环境调控

Microenvironmental regulation of tumour angiogenesis

原文发布日期：2017-07-14

DOI: 10.1038/nrc.2017.51

类型: Review Article

开放获取: 否

要点：

1. Malignant progression of benign tumours is typically associated with an angiogenic switch — the transition from a quiescent to a proliferative vasculature. The de novo recruitment of various innate immune cells was shown to trigger the angiogenic switch in mouse tumour models.
2. Macrophages are important pro-angiogenic cells in the tumour microenvironment. They promote tumour angiogenesis mainly by secreting pro-angiogenic growth factors and facilitating the degradation of the perivascular extracellular matrix.
3. Neutrophils and immature myeloid cells have important roles during the initial angiogenic switch in experimental tumour models. They were also found to sustain tumour revascularization in the context of anti-angiogenic therapy.
4. B cells and T cells may either promote or limit tumour angiogenesis depending on the specific subtype and activation state. In the context of immunotherapy, they may induce the regression of tumour blood vessels.
5. Tumour blood vessels typically display scant pericyte coverage. However, pericytes provide pro-survival cues to angiogenic blood vessels, and their pharmacological targeting improves tumour response to anti-angiogenic therapy.
6. Cancer-associated fibroblasts produce the extracellular matrix and are an important source of pro-angiogenic factors and myeloid cell chemoattractants in the tumour microenvironment.
7. Adipocytes stimulate peri-tumoural angiogenesis by secreting pro-inflammatory and pro-angiogenic cytokines, and by releasing fatty acids that are consumed by angiogenic endothelial cells.
8. The extracellular matrix conveys both pro-angiogenic and angiostatic signals to tumour blood vessels.
9. The metabolic properties of cancer cells and tumour-associated stromal cells influence angiogenesis in many ways (for example, by regulating glucose bioavailability to angiogenic blood vessels).
10. Vascular heterogeneity is a hallmark of cancer and is determined by multiple factors, including the specific organ and tissue in which the tumour arises, the composition of tumour-associated stromal cells, as well as the nature, diversity and relative abundance of pro- and anti-angiogenic mediators.
11. Tumour-associated stromal cells modulate tumour responses to anti-angiogenic therapy.

要点翻译：

1. 良性肿瘤的恶性进展通常与血管生成开关相关——即从静息态血管系统向增殖态血管系统的转变。在小鼠肿瘤模型中发现，多种先天性免疫细胞的从头募集会触发血管生成开关。
2. 巨噬细胞是肿瘤微环境中重要的促血管生成细胞。它们主要通过分泌促血管生成生长因子并促进血管周围细胞外基质的降解来驱动肿瘤血管生成。
3. 在实验性肿瘤模型中，中性粒细胞和未成熟髓样细胞在初始血管生成开关阶段发挥重要作用。研究还发现它们能在抗血管生成治疗中维持肿瘤血管再生。
4. B细胞与T细胞依据特定亚型及活化状态的不同，既可促进也可抑制肿瘤血管生成。在免疫治疗中，它们可能诱导肿瘤血管消退。
5. 肿瘤血管通常表现为周细胞覆盖不足。但周细胞能为生成中的血管提供促生存信号，对其进行药物靶向可提升肿瘤对抗血管生成治疗的反应。
6. 癌症相关成纤维细胞负责产生细胞外基质，同时是肿瘤微环境中促血管生成因子和髓系细胞趋化因子的重要来源。
7. 脂肪细胞通过分泌促炎性细胞因子和促血管生成细胞因子，并释放可被血管生成内皮细胞摄取的脂肪酸，刺激肿瘤周围血管生成。
8. 细胞外基质同时向肿瘤血管传递促血管生成和血管静止信号。
9. 癌细胞及肿瘤相关基质细胞的代谢特性通过多种方式影响血管生成（例如通过调节葡萄糖对生成中血管的生物可利用度）。
10. 血管异质性是癌症的重要特征，其由多种因素决定，包括肿瘤发生的特定器官和组织、肿瘤相关基质细胞的构成，以及促血管生成与抗血管生成介质的性质、多样性和相对丰度。
11. 肿瘤相关基质细胞调节肿瘤对抗血管生成治疗的反应。

英文摘要：

Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and their bioactive products, which encompass cytokines and growth factors, the extracellular matrix and secreted microvesicles. In this Review, we discuss the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.

摘要翻译： 

肿瘤在血管生成模式及特性，以及对抗血管生成疗法的反应上，均表现出显著差异。肿瘤组织的血管生成编程是一个多维度过程，由癌细胞与多种肿瘤相关基质细胞及其生物活性产物（包括细胞因子、生长因子、细胞外基质和分泌微囊泡）共同调控。本综述探讨肿瘤微环境对血管生成的外在调控机制，并指出潜在弱点，这些弱点可作为靶点，以提升抗血管生成癌症治疗的适用性和覆盖范围。

原文链接：

Microenvironmental regulation of tumour angiogenesis