2012年8月13日 讯 /生物谷BIOON/ --近日，PLoS One杂志是上发表的一则研究表明M2巨噬细胞是如何促进肿瘤发展的这已在体内模型中得到验证，在某些类型肿瘤中巨噬细胞的存在与患者临床疗效差有一定的联系。
依靠体外仿真模仿TAMs促进肿瘤进展的模型，在临床开发针对肿瘤相关巨噬细胞（TAMs）的新疗法是必需的。在体外生成和激活的人单核细胞源性巨噬细胞（MDM）分别具有杀伤肿瘤和促进肿瘤两种不同的功能，这归功于巨噬细胞具有两种表型，M1型或M2型巨噬细胞。
在这项研究中，他们比较了来源于单核细胞的巨噬细胞在无血清培养基加M-CSF或GM-CSF和细胞因子如IL-4、IL-10或是IFN-γ、LPS培养以及含血清加M-CSF或GM-CSF培养两种情况下的特性。其中加M-CSF用来特异性诱导M2型巨噬细胞，GM-CSF用来作用于M1型巨噬细胞，IL-4、IL-10用来巨噬细胞激活转变成M2型，IFN-γ与LPS用来生成激活M2型巨噬细胞。
在含血清培养下，科研人员观察到细胞形态发生了差异以及表面受体表达水平的增加，在无血清培养条件下研究人员检测到类似或更高水平的细胞因子生成水平。更重要的是在无血清条件下，MDM分化成M1型巨噬细胞后显现出更强的肿瘤杀伤活性，M2型巨噬细胞促进肿瘤的作用要在有血清培养条件下MDM分化后才能获得。此外，在无血清条件下MDM吞噬活性评价结果相比，M2的吞噬活性强于M1型巨噬细胞。因此，研究数据证实M2型巨噬细胞在体外具有肿瘤促进作用，提示开发靶向TAMs的癌症治疗手段是有依据的。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0042656
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In Vitro Generation of Monocyte-Derived Macrophages under Serum-Free Conditions Improves Their Tumor Promoting Functions
Flora Rey-Giraud1,2, Mathias Hafner2, Carola H. Ries1*
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.
