Influence of tumor cell culture supernatants on macrophage functional polarization: in vitro models of macrophage-tumor environment interaction
Influence of tumor cell culture supernatants on macrophage functional polarization: in vitro models of macrophage-tumor environment interaction
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DOI：
10.1700/989.10726
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发表时间：
2011-09-01
期刊：
影响因子：
1.9
通讯作者：
Salageanu, Aurora
中科院分区：
文献类型：
--
作者：
Caras, Iuliana;Tucureanu, Catalin;Salageanu, Aurora
目标和背景。巨噬细胞是具有广泛功能可塑性的异质细胞;它们可以在极端表型程序（分别标记为M1和M2极化）之间的任何地方重复改变其功能概况以响应环境变化。就抗肿瘤免疫反应而言，M1巨噬细胞被认为是有益的，而M2巨噬细胞据称促进肿瘤进展。肿瘤相关巨噬细胞（TAM）代表了许多肿瘤中存在的主要白细胞群体。尽管许多研究表明TAM引起几种M2相关的促肿瘤功能，包括促进血管生成、基质重塑和抑制适应性免疫，但它们在肿瘤进展方面的作用仍有争议。本研究的目的是建立一个合适的体外模型来研究肿瘤分泌的可溶性因子对巨噬细胞功能表型的影响。将THP-1人单核细胞系细胞和来自健康志愿者的外周血单核细胞用于巨噬细胞分化;将原代肿瘤细胞培养上清液或肿瘤细胞系上清液与各种细胞因子、生长因子和其他刺激物一起使用沿着以设计不同的模型变体并更好地模拟体内肿瘤微环境。这些巨噬细胞的细胞因子分泌模式表明，原代肿瘤细胞培养上清液能够转换巨噬细胞表型或诱导巨噬细胞向M1/M2混合表型的功能极化。这些数据支持TAM行为受肿瘤微环境本身调节的假设。
Aims and background. Macrophages are heterogeneous cells with extensive functional plasticity; they can change their functional profiles repeatedly in response to environmental changes anywhere between their extreme phenotypical programs (labeled as M1 and M2 polarization, respectively). In terms of antitumoral immune response, M1 macrophages are considered to be beneficial, while M2 macrophages supposedly promote tumor progression. Tumor-associated macrophages (TAMs) represent a major leukocyte population present in many tumors. Although many studies indicate that TAMs elicit several M2-associated protumoral functions, including promotion of angiogenesis, matrix remodeling and suppression of adaptive immunity, their role regarding tumor progression is still controversial. The aim of the present study was to develop an appropriate in vitro model to study the effect of tumor-secreted soluble factors on the functional phenotype of macrophages.Methods and study design. THP-1 human monocytic line cells and peripheral blood mononuclear cells from healthy volunteers were used for macrophage differentiation; primary tumor cell culture supernatants or tumor cell line supernatants were employed along with various cytokines, growth factors and other stimuli to design different model variants and to better mimic the in vivo tumor microenvironment.Results. The cytokine secretion patterns of these macrophages suggest that primary tumor cell culture supernatants are able to switch the macrophage phenotype or to induce functional polarization of macrophages toward a mixed M1/M2 phenotype.Conclusions. These data support the hypothesis that TAM behavior is modulated by the tumor microenvironment itself.