Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro.
Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro.
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DOI：
10.1186/s12906-015-0650-3
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发表时间：
2015-04-24
影响因子：
--
通讯作者：
Weissenstein U
中科院分区：
文献类型：
--
作者：
Estko M;Baumgartner S;Urech K;Kunz M;Regueiro U;Heusser P;Weissenstein U
巨噬细胞是一种在肿瘤微环境中发挥重要作用的多功能细胞。肿瘤相关巨噬细胞（tumor associated macrophages, tam）的数量、组成和极化与多种癌症的预后好坏都有关系。粘album亲脂提取物（VALE）含有几种已知可调节单核细胞和其他免疫细胞活性并具有抗癌特性的五环三萜。在我们的体外研究中，我们研究了肿瘤细胞系对巨噬细胞极化和单核细胞趋化迁移的影响，并研究了VALE及其主要的三萜齐墩果酸（OA）的调节潜力。人外周血单核细胞通过M-CSF分化为单核细胞源性巨噬细胞（MDM），通过IFN-γ和LPS分化为M1，通过IL-4和IL-13或与两种不同肿瘤细胞系共培养分化为M2。随后用VALE或OA治疗极化巨噬细胞。通过流式细胞术和免疫分析评估表型标记物和细胞因子。在趋化性迁移实验中，测定了不同肿瘤细胞系在VALE或OA作用下单核细胞趋化蛋白-1 （MCP-1）或上清诱导的人外周血单核细胞的迁移。体外极化的M1和M2型巨噬细胞显示出特定的表型模式，而共培养的MDM肿瘤细胞与M1和M2相关标记物表现出模糊的表型。VALE和OA对肿瘤细胞共培养巨噬细胞的细胞表面标记谱和细胞因子表达有适度影响。所有肿瘤细胞上清液均显著增强了单核细胞的迁移活性。VALE和OA显著抑制MCP-1诱导的单核细胞迁移，而肿瘤细胞衍生的上清液诱导的单核细胞迁移不受影响。在我们的研究中，我们再次证实，与不同的肿瘤细胞系共培养可以导致巨噬细胞M1和M2模式的混合表型，这一发现对于更好地理解肿瘤微环境功能非常重要。此外，我们证明了VALE对肿瘤细胞共培养的巨噬细胞有轻微的免疫调节作用，并在体外调节单核细胞趋化转运，这表明Viscum album L.中的三萜在未来抗癌治疗的多模式概念中有很大的可能性。我们的数据有助于了解体外单核细胞功能和巨噬细胞极化，以及含有槲寄生三萜提取物影响其行为的可能性。
Macrophages are highly versatile cells that play an important role in tumour microenvironment. Tumour associated macrophages (TAMs) have been linked to both, good or bad prognosis of several cancer types depending on their number, composition and polarization. Viscum album lipophilic extract (VALE) contains several pentacyclic triterpenes known to modulate the activity of monocytes and other immune cells and to exhibit anticancer properties. In our in vitro study, we investigated the effect of tumour cell lines on macrophage polarization and monocyte chemotactic transmigration and examined the modulatory potential of VALE and its predominant triterpene oleanolic acid (OA). Human peripheral blood monocytes were differentiated into monocyte derived macrophages (MDM) using M-CSF and polarized into M1 by IFN-γ and LPS and into M2 macrophages by IL-4 and IL-13 or by co-culture with two different tumour cell lines. Polarized macrophages were subsequently treated with VALE or OA. Phenotypic markers and cytokines were assessed by flow cytometry and immunoanalysis. Migration of human peripheral blood monocytes induced by monocyte chemotactic protein-1 (MCP-1) or supernatants of different tumour cell lines under the influence of VALE or OA was measured in a chemotaxis transmigration assay. In vitro polarized M1 and M2 type macrophages revealed specific phenotypic patterns and tumour cell co-cultured MDM displayed ambiguous phenotypes with M1 as well as M2 associated markers. VALE and OA showed modest influence on cell surface marker profile and cytokine expression of tumour cell co-cultured macrophages. All tumour cell supernatants markedly enhanced the migratory activity of monocytes. VALE and OA significantly inhibited MCP-1 induced monocyte transmigration, whereas monocyte migration initiated by tumour cell derived supernatants was not affected. In our study we reconfirmed that co-culture with different tumour cell lines can result in a mixed macrophage phenotype with M1 as well as M2 patterns, a finding that is important for a better understanding of tumour microenvironment functions. Moreover, we demonstrated that VALE shows slight immunomodulatory effects on tumour cell co-cultured macrophages and modulates monocyte chemotactic transmigration in vitro, indicating promising possibilities of triterpenes from Viscum album L. to contribute in a multimodal concept of anti-cancer therapy in future. Our data contribute to an understanding of monocyte function and macrophage polarization in vitro and of the possibility to influence their behaviour by triterpene containing mistletoe extracts.
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影响因子：
7.2
作者：
Bögels M;Braster R;Nijland PG;Gül N;van de Luijtgaarden W;Fijneman RJ;Meijer GA;Jimenez CR;Beelen RH;van Egmond M
通讯作者：
van Egmond M
影响因子：
1.9
作者：
Caras, Iuliana;Tucureanu, Catalin;Salageanu, Aurora
通讯作者：
Salageanu, Aurora
DOI：
10.1007/bf01865469
发表时间：
1938-01-01
影响因子：
--
作者：
Janssen, S
通讯作者：
Janssen, S
影响因子：
6.4
作者：
BOTTAZZI, B;GHEZZI, P;MANTOVANI, A
通讯作者：
MANTOVANI, A
影响因子：
11.4
作者：
Legdeur, MCJC;Beelen, RHJ;Ossenkoppele, GJ
通讯作者：
Ossenkoppele, GJ