Macrophage migration inhibitory factor produced by the tumour stroma but not by tumour cells regulates angiogenesis in the B16-F10 melanoma model.
Macrophage migration inhibitory factor produced by the tumour stroma but not by tumour cells regulates angiogenesis in the B16-F10 melanoma model.
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DOI：
10.1038/bjc.2012.392
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发表时间：
2012-10-23
影响因子：
8.8
通讯作者：
Queva, C.
中科院分区：
文献类型：
--
作者：
Girard, E.;Strathdee, C.;Trueblood, E.;Queva, C.
巨噬细胞移动抑制因子（MIF）已被提出作为炎症和肿瘤发生之间的联系。尽管其在肿瘤生物学和普遍表达中的潜在广泛影响，但MIF作为癌症治疗靶点的价值仍不清楚。我们试图通过完全抑制MIF在肿瘤细胞和肿瘤间质中的表达来验证MIF在肿瘤模型中的作用。我们使用MIF shRNA转导的B16-F10黑色素瘤细胞植入野生型和MIF−/− C57 B16小鼠，以研究MIF缺失对肿瘤生长的影响。细胞因子检测和免疫组织化学（IHC）用于评价肿瘤离体。巨噬细胞移动抑制因子shRNA抑制B16-F10黑色素瘤细胞MIF蛋白表达的实验研究在体外实验中，该细胞系中MIF的缺失导致对缺氧的反应降低，如VEGF表达降低所示。在体内，与野生型相比，MIF−/−小鼠中B16-F10肿瘤的生长平均抑制47%，但不受肿瘤细胞失去MIF表达的影响。免疫组织化学分析显示，植入MIF−/−小鼠的肿瘤中微血管密度降低。血清细胞因子谱显示MIF−/−小鼠中促血管生成细胞因子减少。我们报告说，在主机中的MIF的情况下，导致肿瘤生长较慢，这是与减少血管。虽然MIF的主要贡献似乎是在调节血管生成，肿瘤细胞衍生的MIF在这个过程中发挥了微不足道的作用。
Macrophage migration inhibitory factor (MIF) has been proposed as a link between inflammation and tumorigenesis. Despite its potentially broad influence in tumour biology and prevalent expression, the value of MIF as a therapeutic target in cancer remains unclear. We sought to validate MIF in tumour models by achieving a complete inhibition of its expression in tumour cells and in the tumour stroma. We used MIF shRNA-transduced B16-F10 melanoma cells implanted in wild-type and MIF−/− C57Bl6 mice to investigate the effect of loss of MIF on tumour growth. Cytokine detection and immunohistochemistry (IHC) were used to evaluate tumours ex vivo. Macrophage migration inhibitory factor shRNA inhibited expression of MIF protein by B16-F10 melanoma cells in vitro and in vivo. In vitro, the loss of MIF in this cell line resulted in a decreased response to hypoxia as indicated by reduced expression of VEGF. In vivo the growth of B16-F10 tumours was inhibited by an average of 47% in the MIF−/− mice compared with wild-type but was unaffected by loss of MIF expression by the tumour cells. Immunohistochemistry analysis revealed that microvessel density was decreased in tumours implanted in the MIF−/− mice. Profiling of serum cytokines showed a decrease in pro-angiogenic cytokines in MIF−/− mice. We report that the absence of MIF in the host resulted in slower tumour growth, which was associated with reduced vascularity. While the major contribution of MIF appeared to be in the regulation of angiogenesis, tumour cell-derived MIF played a negligible role in this process.
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DOI：
10.1084/jem.190.10.1375
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hudson JD;Shoaibi MA;Maestro R;Carnero A;Hannon GJ;Beach DH
通讯作者：
Beach DH
影响因子：
4.4
作者：
Abe, R;Peng, T;Metz, CN
通讯作者：
Metz, CN
影响因子：
32.4
作者：
Bucala, Richard;Donnelly, Seamas C.
通讯作者：
Donnelly, Seamas C.
影响因子：
5.2
作者：
Culp, W. David;Tsagozis, Panagiotis;Garland, Donita
通讯作者：
Garland, Donita
影响因子：
4.4
作者：
Meyer-Siegler, Katherine L.;Iczkowski, Kenneth A.;Vera, Pedro L.
通讯作者：
Vera, Pedro L.