In vitro generation of monocyte-derived macrophages under serum-free conditions improves their tumor promoting functions.
In vitro generation of monocyte-derived macrophages under serum-free conditions improves their tumor promoting functions.
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DOI：
10.1371/journal.pone.0042656
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ries CH
中科院分区：
文献类型：
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作者：
Rey-Giraud F;Hafner M;Ries CH
在体内模型中描述了M2巨噬细胞的肿瘤促进作用，并且在某些肿瘤类型中存在巨噬细胞与不良临床结局有关。鉴于临床上开发靶向肿瘤相关巨噬细胞（TAM）的新疗法的新兴活动，需要忠实地模拟TAM的肿瘤促进功能的可靠体外模型。体外人单核细胞源性巨噬细胞（MDM）的产生和活化，分别被描述为具有杀肿瘤或促肿瘤功能的M1或M2巨噬细胞，已被广泛报道，主要使用含血清的培养方法。在这项研究中，我们比较了来源于单核细胞的巨噬细胞的性质，这些单核细胞在含有血清的培养基中与M-CSF（M2）和GM-CSF（M1）一起培养，或者在补充有M-CSF或GM-CSF和细胞因子（如IL-4、IL-10）的无血清培养基中诱导活化的M2或LPS与IFN-γ一起产生活化的M1表型。我们观察到细胞形态的差异，以及增加的表面受体表达水平在含血清的培养，而类似或更高的细胞因子的生产水平下检测无血清培养条件。更重要的是，与在血清存在下分化的MDM相比，在无血清条件下分化的MDM显示出增强的M1杀肿瘤活性和M2巨噬细胞的肿瘤促进特性。此外，在无血清条件下对MDM吞噬活性的评价表明，M2的吞噬特性大于M1。因此，我们的数据证实了M2巨噬细胞在体外的肿瘤促进特性，并鼓励靶向TAM用于癌症治疗。
The tumor promoting role of M2 macrophages has been described in in vivo models and the presence of macrophages in certain tumor types has been linked to a poor clinical outcome. In light of burgeoning activities to clinically develop new therapies targeting tumor-associated macrophages (TAMs), reliable in vitro models faithfully mimicking the tumor promoting functions of TAMs are required. Generation and activation of human monocyte-derived macrophages (MDM) in vitro, described as M1 or M2 macrophages attributed with tumoricidal or tumor-promoting functions, respectively, has been widely reported using mainly serum containing culture methods. In this study, we compared the properties of macrophages originating from monocytes cultured either in media containing serum together with M-CSF for M2 and GM-CSF for M1 macrophages or in serum-free media supplemented with M-CSF or GM-CSF and cytokines such as IL-4, IL-10 to induce activated M2 or LPS together with IFN-γ to generate activated M1 phenotype. We observed differences in cell morphology as well as increased surface receptor expression levels in serum-containing culture whereas similar or higher cytokine production levels were detected under serum-free culture conditions. More importantly, MDM differentiated under serum-free conditions displayed enhanced tumoricidal activity for M1 and tumor promoting property for M2 macrophages in contrast to MDM differentiated in the presence of serum. Moreover, evaluation of MDM phagocytic activity in serum free condition resulted in greater phagocytic properties of M2 compared to M1. Our data therefore confirm the tumor promoting properties of M2 macrophages in vitro and encourage the targeting of TAMs for cancer therapy.
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影响因子：
5.4
作者：
Recalcati, Stefania;Locati, Massimo;Cairo, Gaetano
通讯作者：
Cairo, Gaetano
影响因子：
20.3
作者：
Delneste, Y;Charbonnier, P;Jeannin, P
通讯作者：
Jeannin, P
DOI：
10.3324/haematol.2010.031542
发表时间：
2011-02-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Kamper, Peter;Bendix, Knud;d'Amore, Francesco
通讯作者：
d'Amore, Francesco
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/nri3070
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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