The macrophage migration inhibitory factor (MIF)-homologue D-dopachrome tautomerase is a therapeutic target in a murine melanoma model.
The macrophage migration inhibitory factor (MIF)-homologue D-dopachrome tautomerase is a therapeutic target in a murine melanoma model.
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DOI：
10.18632/oncotarget.1560
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发表时间：
2014-01-15
期刊：
影响因子：
--
通讯作者：
Endres S
中科院分区：
文献类型：
--
作者：
Kobold S;Merk M;Hofer L;Peters P;Bucala R;Endres S
巨噬细胞移动抑制因子(MIF)同系物D-多巴色素互变酶(D-DT)最近被描述为具有与MIF相似的功能。然而，与MIF相反，D-DT在肿瘤生物学中的作用仍不清楚。我们假设D-DT可以作为癌症治疗干预的靶点。我们用Western印迹和ELISA法分析了小鼠黑色素瘤模型B16F10和小鼠乳腺癌模型4T1中D-DT的产生。肿瘤细胞在体内外均可释放D-DT。RT-PCR结果显示D-DT受体CD74在两种肿瘤细胞系中均有表达。与健康对照组相比，荷瘤小鼠的血清D-DT水平更高。流式细胞仪显示，在BrDU实验中，siRNA下调D-dt基因使B16F10细胞的增殖减少，并使其更容易诱导凋亡。在体内，抗体中和D-DT可减少B16F10皮下同基因肿瘤模型中的肿瘤进展。综上所述，我们可以证明D-DT及其受体在小鼠肿瘤B16F10和4T1中表达。通过siRNA或抗体阻断D-DT可抑制B16F10肿瘤细胞的增殖。这使D-DT有资格作为治疗靶点进行进一步评估。
The macrophage migration inhibitory factor (MIF)-homologue D- dopachrome tautomerase (D-DT) recently has been described to have similar functions as MIF. However, the role of D-DT, as opposed to MIF, in tumor biology remains unknown. We hypothesized that D-DT could represent a target for therapeutic interventions in cancer. We analyzed the production of D-DT in the murine melanoma model B16F10 and the murine breast cancer model 4T1 by western blot and ELISA. D-DT was released by tumor cells both in vitro and in vivo. RT-PCR revealed the expression of the D-DT receptor CD74 on both tumor cell lines. Tumor bearing mice had higher serum levels of D-DT compared to healthy controls. Remarkably, knock-down of D-DT by siRNA reduced proliferation of B16F10 cells in BrDU-assay and rendered them more prone to apoptosis induction, as shown by flow cytometry. In vivo neutralization of D-DT by antibodies reduced tumor progression in the B16F10 subcutaneous syngeneic tumor model. In summary, we could show that D-DT and its receptor are expressed in the murine tumors B16F10 and 4T1. Knock-down of D-DT through siRNA or blocking by antibodies reduced proliferation of B16F10 tumor cells. This qualifies D-DT for further evaluation as a therapeutic target.
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DOI：
10.4049/jimmunol.181.4.2330
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Coleman AM;Rendon BE;Zhao M;Qian MW;Bucala R;Xin D;Mitchell RA
通讯作者：
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影响因子：
32.4
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Donnelly, Seamas C.
DOI：
10.3324/haematol.2009.014464
发表时间：
2010-05-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
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作者：
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Kroeger, Nicolaus
DOI：
10.1111/j.1365-2613.2007.00539.x
发表时间：
2007-10-01
影响因子：
3
作者：
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通讯作者：
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DOI：
10.4049/jimmunol.1201650
发表时间：
2013-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yaddanapudi K;Putty K;Rendon BE;Lamont GJ;Faughn JD;Satoskar A;Lasnik A;Eaton JW;Mitchell RA
通讯作者：
Mitchell RA