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小眼畸形相关转录因子（MITF）调控免疫细胞向黑色素瘤的迁移。

Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma.

作者信息

Wiedemann Gabriela M, Aithal Celina, Kraechan Angelina, Heise Constanze, Cadilha Bruno L, Zhang Jin, Duewell Peter, Ballotti Robert, Endres Stefan, Bertolotto Corine, Kobold Sebastian

机构信息

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Klinikum der Universität München, Lindwurmstrasse 2a, 80337 Munich, Germany; Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Germany.

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Klinikum der Universität München, Lindwurmstrasse 2a, 80337 Munich, Germany.

出版信息

Transl Oncol. 2019 Feb;12(2):350-360. doi: 10.1016/j.tranon.2018.10.014. Epub 2018 Nov 28.

DOI:10.1016/j.tranon.2018.10.014
PMID:30502589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6290759/
Abstract

Microphthalmia-associated transcription factor (MITF) is a key transcription factor in melanoma development and progression. MITF amplification and downregulation have been observed in a significant proportion of melanoma patients and correlate with clinical outcomes. Here, we have investigated the effect of MITF on melanoma chemokine expression and immune cell attraction. In B16F10 melanoma cells, MITF knockdown reduced expression of CXCL10, with concomitantly decreased attraction of immune cells and accelerated tumor outgrowth. Conversely, overexpression of MITF in YUMM1.1 melanoma cells also led to an increased immune cell attraction in vitro. Subcutaneous YUMM1.1 melanomas overexpressing MITF however showed a reduced immune infiltration of lymphocytes and an increased tumor growth. In human melanoma cell lines, silencing of MITF enhanced chemokine production and immune cell attraction, while overexpression of MITF led to lower immune cell attraction. In summary, our results show that MITF regulates chemokine expression in murine and in human melanoma cells, and affects in vivo immune cell attraction and tumor growth. These results reveal a functional relationship between MITF and immune cell infiltration, which may be exploited for cancer therapy.

摘要

小眼畸形相关转录因子（MITF）是黑色素瘤发生发展过程中的关键转录因子。在相当比例的黑色素瘤患者中观察到MITF扩增和下调，且与临床预后相关。在此，我们研究了MITF对黑色素瘤趋化因子表达和免疫细胞吸引的影响。在B16F10黑色素瘤细胞中，MITF敲低降低了CXCL10的表达，同时减少了免疫细胞的吸引并加速了肿瘤生长。相反，YUMM1.1黑色素瘤细胞中MITF的过表达在体外也导致免疫细胞吸引增加。然而，过表达MITF的皮下YUMM1.1黑色素瘤显示淋巴细胞的免疫浸润减少且肿瘤生长增加。在人黑色素瘤细胞系中，MITF沉默增强了趋化因子的产生和免疫细胞吸引，而MITF过表达导致免疫细胞吸引降低。总之，我们的结果表明，MITF调节小鼠和人黑色素瘤细胞中的趋化因子表达，并影响体内免疫细胞吸引和肿瘤生长。这些结果揭示了MITF与免疫细胞浸润之间的功能关系，这可能被用于癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/5685ff1c5211/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/1f570a6578ac/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/710879a71ac2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/b5b705369820/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/83de6deeca93/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/9912db8fd02e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/520af615e345/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/c6192bf518c3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/5685ff1c5211/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/1f570a6578ac/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/710879a71ac2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/b5b705369820/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/83de6deeca93/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/9912db8fd02e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/520af615e345/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/c6192bf518c3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9485/6290759/5685ff1c5211/gr8.jpg

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MITF suppression improves the sensitivity of melanoma cells to a BRAF inhibitor.MITF 抑制可提高黑色素瘤细胞对 BRAF 抑制剂的敏感性。
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