文章：

骨髓细胞在促进肿瘤血管生成中的作用

The role of myeloid cells in the promotion of tumour angiogenesis

原文发布日期：2008-07-17

DOI: 10.1038/nrc2444

类型: Review Article

开放获取: 否

要点：

1. Bone marrow-derived myeloid cells such as macrophages, neutrophils, eosinophils, mast cells and dendritic cells infiltrate malignant tumours in large numbers and are sometimes a prominent feature in the stroma of such tissues.
2. A wide array of chemoattractants released by both malignant and stromal cells in tumours recruit myeloid cells from the tumour vasculature into tumours.
3. Recent studies have shown these cells not only to be central in the regulation of inflammatory events and various immune mechanisms but also to have an important role in driving various crucial processes in tumorigenesis, including angiogenesis.
4. Their role in tumour progression is often multifaceted and includes the production of pro-angiogenic growth factors and vascular-modulating enzymes. It may also extend to their possible trans-differentiation into endothelial cells in response to prolonged pro-angiogenic stimuli in tumours.
5. Signals produced within the tumour microenvironment appear to stimulate many of the pro-angiogenic functions of these cells. For example, tumour-infiltrating macrophages are stimulated to act as a potent pro-angiogenic force in tumours by exposure to tumour hypoxia and/or such tumour cell-derived cytokines as vascular endothelial growth factor (VEGF), tumour necrosis factor α and angiopoietin 2.
6. Antibodies (and other inhibitors) that block the uptake of pro-angiogenic myeloid cells such as monocytes into tumours are now being developed and tested in preclinical mouse models. For example, a neutralizing antibody to CCL2 markedly reduces both the number of tumour-associated macrophages and tumour angiogenesis.
7. Some subpopulations of myeloid cells inhibit the anti-angiogenic response of tumours to antibodies targeting VEGF and placental growth factor in tumours. They have also been implicated in tumour responses to chemotherapy or radiation therapy.

要点翻译：

1. 骨髓来源的髓系细胞（如巨噬细胞、中性粒细胞、嗜酸性粒细胞、肥大细胞和树突状细胞）会大量浸润恶性肿瘤，有时甚至成为此类组织间质中的显著特征。
2. 肿瘤中恶性细胞与基质细胞释放的多种趋化因子，将这些髓系细胞从肿瘤血管系统招募至肿瘤内部。
3. 最新研究表明，这些细胞不仅核心调控炎症事件及多种免疫机制，更在驱动肿瘤发生的关键进程中发挥重要作用，包括血管生成。
4. 它们在肿瘤进展中的作用常具多面性：既产生促血管生成生长因子与血管调节酶，又可能在长期促血管生成刺激下通过转分化形成内皮细胞。
5. 肿瘤微环境中的信号似乎能激活这些细胞的多种促血管生成功能。例如，浸润肿瘤的巨噬细胞在接触肿瘤低氧环境和/或肿瘤源性细胞因子（如血管内皮生长因子、肿瘤坏死因子α、血管生成素2）后，会被激活成为强效促血管生成因子。
6. 目前正在开发能阻断单核细胞等促血管生成髓系细胞进入肿瘤的抗体（及其他抑制剂），并在临床前小鼠模型中进行测试。例如，CCL2中和抗体可显著减少肿瘤相关巨噬细胞数量并抑制肿瘤血管生成。
7. 某些髓系细胞亚群会抑制肿瘤对靶向VEGF与胎盘生长因子抗体的抗血管生成反应。它们还与肿瘤对化疗或放疗的治疗反应密切相关。

英文摘要：

The use of various transgenic mouse models and analysis of human tumour biopsies has shown that bone marrow-derived myeloid cells, such as macrophages, neutrophils, eosinophils, mast cells and dendritic cells, have an important role in regulating the formation and maintenance of blood vessels in tumours. In this Review the evidence for each of these cell types driving tumour angiogenesis is outlined, along with the mechanisms regulating their recruitment and activation by the tumour microenvironment. We also discuss the therapeutic implications of recent findings that specific myeloid cell populations modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies.

摘要翻译： 

利用多种转基因小鼠模型和人肿瘤活检分析已证实，骨髓来源的髓系细胞（如巨噬细胞、中性粒细胞、嗜酸性粒细胞、肥大细胞和树突状细胞）在调控肿瘤血管的形成与维持中发挥重要作用。本文综述了这些细胞类型驱动肿瘤血管生成的证据，以及肿瘤微环境对其招募和激活的调控机制。我们还探讨了近期发现的临床意义：特定髓系细胞群可调节肿瘤对化疗及某些抗血管生成治疗的反应。

原文链接：

The role of myeloid cells in the promotion of tumour angiogenesis