The role of tumor-associated macrophages in tumor vascularization.
The role of tumor-associated macrophages in tumor vascularization.
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DOI：
10.1186/2045-824x-5-20
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发表时间：
2013-12-06
期刊：
影响因子：
--
通讯作者：
Wang XY
中科院分区：
文献类型：
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作者：
Guo C;Buranych A;Sarkar D;Fisher PB;Wang XY
肿瘤血管生成是一个高度复杂的过程，涉及肿瘤与周围间质以及多种不同的血管生成调节因子之间的相互作用。肿瘤相关巨噬细胞(TAMs)是肿瘤环境中含量最丰富的细胞成分之一，也是癌症相关炎症的关键因素。大量证据支持TAMS在促进异常肿瘤血管网络的形成以及随后的肿瘤进展和侵袭中起关键作用的观点。临床和实验证据表明，高水平的浸润性TAM与患者预后不良和肿瘤对治疗的耐药性有关。除了刺激肿瘤生长过程中的血管生成外，TAMs还能在细胞毒治疗(如放射治疗)后促进肿瘤血管的重新形成，从而导致癌症复发。在这篇综述中，我们重点介绍了与肿瘤微环境中TAMs的表型和极化相关的新数据，以及巨噬细胞在调节血管生成开关和肿瘤血管形成中的潜在机制。此外，我们还讨论了靶向促血管生成TAMs的可能性，或将TAMs重新编程为杀瘤和抑血管表型，以促进肿瘤血管的正常化，以提高癌症治疗的结果。
Tumor vascularization is a highly complex process that involves the interaction between tumors and their surrounding stroma, as well as many distinct angiogenesis-regulating factors. Tumor associated macrophages (TAMs) represent one of the most abundant cell components in the tumor environment and key contributors to cancer-related inflammation. A large body of evidence supports the notion that TAMs play a critical role in promoting the formation of an abnormal tumor vascular network and subsequent tumor progression and invasion. Clinical and experimental evidence has shown that high levels of infiltrating TAMs are associated with poor patient prognosis and tumor resistance to therapies. In addition to stimulating angiogenesis during tumor growth, TAMs enhance tumor revascularization in response to cytotoxic therapy (e.g., radiotherapy), thereby causing cancer relapse. In this review, we highlight the emerging data related to the phenotype and polarization of TAMs in the tumor microenvironment, as well as the underlying mechanisms of macrophage function in the regulation of the angiogenic switch and tumor vascularization. Additionally, we discuss the potential of targeting pro-angiogenic TAMs, or reprograming TAMs toward a tumoricidal and angiostatic phenotype, to promote normalization of the tumor vasculature to enhance the outcome of cancer therapies.