Macrophages define the invasive microenvironment in breast cancer
Macrophages define the invasive microenvironment in breast cancer
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DOI：
10.1189/jlb.1107762
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发表时间：
2008-09-01
影响因子：
5.5
通讯作者：
Pollard, Jeffrey W.
中科院分区：
文献类型：
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作者：
Pollard, Jeffrey W.
在许多人类癌症中，肿瘤微环境中巨噬细胞的丰度与预后不良相关。巨噬细胞和预后不良之间因果关系的实验证据来自乳腺癌小鼠模型，其中巨噬细胞的基因消融导致肿瘤进展和转移的减弱，并且过早募集到增生性病变加速了这些过程。恶性肿瘤的定义是肿瘤细胞侵入基质，这是一个允许这些细胞逃逸到循环中并扩散到远处的过程。在这篇综述中，我认为，巨噬细胞被招募到侵袭性前线的表达肿瘤衍生的趋化因子，并在基底膜的破坏。在该侵袭部位，巨噬细胞通过分泌包括表皮生长因子（EGF）在内的趋化因子和趋化动力学因子来增强肿瘤细胞的迁移和侵袭。它们通过合成血管生成因子（包括血管内皮生长因子（VEGF））来促进血管生成，并且它们重塑细胞外基质，特别是调节胶原纤维形成。这些因素的结合带来了三重打击，因为更具移动的和侵袭性的肿瘤细胞沿着胶原纤维追踪，而胶原纤维也锚定在血管上，这些纤维是在侵袭部位制造的，巨噬细胞通过这些纤维增强肿瘤细胞的侵袭。所有这些活动表明，巨噬细胞的功能是产生新的治疗，应改善目前的细胞毒性医疗设备的重要目标。
In many human cancers, the abundance of macrophages in the tumor microenvironment is correlated with poor prognosis. Experimental evidence for the causal relationship between macrophages and poor prognosis came from mouse models of breast cancer in which genetic ablation of macrophages resulted in attenuation of tumor progression and metastasis, and premature recruitment to hyperplastic lesions accelerated these processes. Malignancy is defined by the invasion of tumor cells into the stroma, a process that allows escape of these cells into the circulation and dissemination to distant sites. In this review, I argue that macrophages are recruited to the invasive front by expression of tumor-derived chemotactic factors and in response to the disruption of the basement membrane. At this invasive site, macrophages enhance tumor cell migration and invasion through their secretion of chemotactic and chemokinetic factors including epidermal growth factor (EGF). They promote angiogenesis by the synthesis of angiogenic factors including vascular endothelial growth factor (VEGF), and they remodel the extracellular matrix and in particular, regulate collagen fibrillogenesis. A combination of these factors provides a triple-whammy, as the more mobile and invasive tumor cells track along collagen fibers that are also anchored to blood vessels, which are fabricated at sites of invasion and through which macrophages potentiate tumor cell intravasation. All of these activities suggest that macrophage functions are significant targets for the generation of novel therapeutics that should improve the current cytotoxic armamentarium.