2012年8月13日 訊 /生物谷BIOON/ --近日,，PLoS One雜志是上發(fā)表的一則研究表明M2巨噬細胞是如何促進腫瘤發(fā)展的這已在體內(nèi)模型中得到驗證,，在某些類型腫瘤中巨噬細胞的存在與患者臨床療效差有一定的聯(lián)系。
依靠體外仿真模仿TAMs促進腫瘤進展的模型,，在臨床開發(fā)針對腫瘤相關(guān)巨噬細胞（TAMs）的新療法是必需的,。在體外生成和激活的人單核細胞源性巨噬細胞（MDM）分別具有殺傷腫瘤和促進腫瘤兩種不同的功能，這歸功于巨噬細胞具有兩種表型,，M1型或M2型巨噬細胞,。
在這項研究中，他們比較了來源于單核細胞的巨噬細胞在無血清培養(yǎng)基加M-CSF或GM-CSF和細胞因子如IL-4、IL-10或是IFN-γ,、LPS培養(yǎng)以及含血清加M-CSF或GM-CSF培養(yǎng)兩種情況下的特性。其中加M-CSF用來特異性誘導M2型巨噬細胞,，GM-CSF用來作用于M1型巨噬細胞,，IL-4、IL-10用來巨噬細胞激活轉(zhuǎn)變成M2型,，IFN-γ與LPS用來生成激活M2型巨噬細胞,。
在含血清培養(yǎng)下，科研人員觀察到細胞形態(tài)發(fā)生了差異以及表面受體表達水平的增加,，在無血清培養(yǎng)條件下研究人員檢測到類似或更高水平的細胞因子生成水平,。更重要的是在無血清條件下，MDM分化成M1型巨噬細胞后顯現(xiàn)出更強的腫瘤殺傷活性,，M2型巨噬細胞促進腫瘤的作用要在有血清培養(yǎng)條件下MDM分化后才能獲得,。此外，在無血清條件下MDM吞噬活性評價結(jié)果相比,，M2的吞噬活性強于M1型巨噬細胞,。因此，研究數(shù)據(jù)證實M2型巨噬細胞在體外具有腫瘤促進作用,，提示開發(fā)靶向TAMs的癌癥治療手段是有依據(jù)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.
