The role of tumor-associated macrophages in breast cancer progression (review).
The role of tumor-associated macrophages in breast cancer progression (review).
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DOI：
10.3892/ijo.2013.1938
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发表时间：
2013-07
影响因子：
5.2
通讯作者：
Olopade OI
中科院分区：
文献类型：
--
作者：
Obeid E;Nanda R;Fu YX;Olopade OI
肿瘤微环境在恶性实体瘤的侵袭行为中起着重要作用。在与肿瘤微环境相关的细胞类型中，肿瘤相关巨噬细胞（TAM）对肿瘤进展影响最大。乳腺癌的特征在于具有大量的TAM，并且实验模型已经揭示了TAM与周围肿瘤细胞相互作用并影响周围肿瘤细胞的多种机制。转移的过程涉及肿瘤细胞进入直接肿瘤环境外的组织并侵入限制性细胞外基质（ECM）。支持这一过程，TAM分泌促血管生成因子，如VEGF，以建立为肿瘤细胞提供营养的血管网络，但也作为转运到ECM中的通道。此外，TAM释放因子以降低局部促炎性抗肿瘤反应，抑制它并提供肿瘤细胞逃逸的手段。类似地，肿瘤微环境中的缺氧刺激巨噬细胞进一步产生VEGF并抑制T细胞免疫应答，从而增强肿瘤细胞的逃避并最终转移。鉴于TAMS在乳腺癌进展和转移中的多重作用，靶向这些细胞的疗法正在开发中，并显示出有希望的结果。
It is well established that the tumor microenvironment plays a major role in the aggressive behavior of malignant solid tumors. Among cell types associated with tumor microenvironment, tumor-associated macrophages (TAMs) are the most influential for tumor progression. Breast cancer is characterized by having a large population of TAMs, and experimental models have exposed multiple mechanisms by which TAMs interact with and influence the surrounding tumor cells. The process of metastasis involves tumor cells gaining access to the tissue outside the immediate tumor environment and invading the confining extracellular matrix (ECM). Supporting this process, TAMs secrete proangiogenic factors such as VEGF to build a network of vessels that provide nutrition for tumor cells, but also function as channels of transport into the ECM. Additionally, TAMs release factors to decrease the local pro-inflammatory antitumor response, suppressing it and providing a means of escape of the tumor cells. Similarly, hypoxia in the tumor microenvironment stimulates macrophages to further produce VEGF and suppress the T-cell immune responses, thus, enhancing the evasion of tumor cells and ultimately metastasis. Given the multiple roles of TAMS in breast cancer progression and metastasis, therapies targeting these cells are in development and demonstrate promising results.
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