Polarization of tumor-associated macrophage is associated with tumor vascular normalization by endostatin
Polarization of tumor-associated macrophage is associated with tumor vascular normalization by endostatin
复制标题
肿瘤相关巨噬细胞的极化与内皮抑素的肿瘤血管正常化相关
DOI：
10.1111/1759-7714.12018
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发表时间：
2013-08-01
期刊：
影响因子：
2.9
通讯作者：
Luo, Feng
中科院分区：
文献类型：
--
作者：
Peng, Qian;Li, Mei;Luo, Feng
背景：血管正常化在癌症治疗中是一个新兴的概念，但其确切机制尚不完全清楚。肿瘤相关巨噬细胞（tumor associated macrophages, tam）的极化在肿瘤血管生成和转移中起重要作用。然而，抗血管生成药物对肿瘤相关巨噬细胞极化的影响知之甚少。因此，我们探讨内皮抑素诱导肿瘤血管正常化发展过程中tam极化的变化。方法：采用内皮抑素治疗小鼠肺癌异种移植模型10 d。采用各种技术检查肿瘤血管的形态和功能。流式细胞术检测TAMs，免疫荧光法检测肿瘤中表达tie -2的单核细胞（tem）。采用免疫组化和Western blot检测肿瘤组织中富组氨酸糖蛋白（HRG）水平。结果：内皮抑素处理小鼠肿瘤血管在第6天变得更加正常和成熟。在血管正常化期间，肿瘤中m2样tam和tem的数量明显减少，而内皮抑素治疗后第6天，m1样tam的数量增加，尽管后者没有统计学意义。内皮抑素给药后，肿瘤内HRG在早期积累。结论：TAMs极化与内皮抑素诱导肿瘤血管正常化有关。这些观察结果可能有助于探索抗血管生成治疗的新策略。
Background: Vascular normalization is an emerging concept in cancer treatment, but its precise mechanisms are not completely understood. The polarization of tumor-associated macrophages (TAMs) is important in tumor angiogenesis and metastasis. However, little is known about the effect of anti-angiogenic agents on the polarization of tumor-associated macrophages. Therefore, we explore the changes of TAMs polarization in the development of tumor vascular normalization induced by endostatin.Methods: A murine xenograft model of lung cancer was treated with endostatin for 10 days. The morphology and function of tumor vasculature was examined using various techniques. Flow cytometry was carried out to assess the TAMs, and immunofluorescence was used to examine Tie-2-expressing monocytes (TEMs) in tumors. Levels of the histidine-rich glycoprotein (HRG) in tumors were measured by immunohistochemistry and Western blot.Results: Tumor vessels became more normal and mature on day six in the endostatin-treated mice. During vascular normalization, the number of M2-like TAMs and TEMs in the tumors was significantly reduced, whereas the number of M1-like TAMs showed an increase on day six after endostatin treatment, although the latter was not statistically significant. The HRG in the tumors accumulated at an early stage after endostatin administration.Conclusions: The polarization of TAMs is associated with tumor vascular normalization induced by endostatin. These observations may be useful in the exploration of new strategies for anti-angiogenic treatment.