LRP2在黑色素瘤中的表达与短暂细胞状态、T细胞浸润增加以及IFNy信号的上调有关

IF 2.6 3区 医学 Q2 CELL BIOLOGY
Martin Q. Rasmussen, Marie L. Bønnelykke-Behrndtz, Camilla Merrild, Ida Tvilling, Julie N. Christensen, Morten M. Nielsen, Jeanette B. Georgsen, Nina Naumann, Johann M. Gudbergsson, Anders Etzerodt, Jakob S. Pedersen, Russell W. Jenkins, Søren E. Degn, Søren K. Moestrup, Henrik Schmidt, Torben Steiniche, Mette Madsen
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引用次数: 0

摘要

低密度脂蛋白受体相关蛋白2 (LRP2)是一种600千道尔顿的多配体内吞膜受体,在胎儿发育期间的几种细胞类型中表达,包括神经上皮细胞,以及成人的某些吸收性上皮细胞。在上皮性癌症中,LRP2表达与分化的肿瘤细胞状态和更好的预后相关。在之前的工作中,我们发现LRP2在良性痣中不表达,但在黑色素瘤中经常获得。然而,黑色素瘤中LRP2表达的分子驱动因素和表达LRP2的黑色素瘤的特征尚未被描述。在这里,我们发现LRP2的表达与黑素细胞谱系和神经嵴转录程序共同表达的短暂性黑色素瘤细胞状态有关。此外,我们发现黑色素瘤LRP2表达在T细胞炎症肿瘤中增加,并通过干扰素- γ信号直接上调。黑色素瘤LRP2表达与临床病理变量的相关性表明,原发性黑色素瘤中LRP2表达与低Breslow厚度和低临床分期相关。综上所述,本研究描述了表达LRP2的黑色素瘤的特征,并揭示了干扰素- γ信号是黑色素瘤中LRP2表达的一种新的强正调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

LRP2 Expression in Melanoma Is Associated With a Transitory Cell State, Increased T Cell Infiltration, and Is Upregulated by IFNy Signaling

LRP2 Expression in Melanoma Is Associated With a Transitory Cell State, Increased T Cell Infiltration, and Is Upregulated by IFNy Signaling

Low density lipoprotein receptor-related protein 2 (LRP2) is a 600 kilodalton multi-ligand endocytic membrane receptor expressed in several cell types during fetal development, including neuroepithelial cells, and in select absorptive epithelial cells in the adult. In epithelial cancers, LRP2 expression is associated with a differentiated tumor cell state and better prognosis. In previous work, we found that while LRP2 is not expressed in benign naevi, it is frequently acquired in melanoma. However, the molecular drivers of LRP2 expression in melanoma and characteristics of LRP2-expressing melanoma have yet to be described. Here, we show that LRP2 expression is related to a transitory melanoma cell state defined by co-expression of melanocyte lineage and neural crest transcriptional programs. Further, we reveal that melanoma LRP2 expression is increased in T cell-inflamed tumors and is directly upregulated through interferon-gamma signaling. Correlation of melanoma LRP2 expression with clinicopathological variables demonstrates that LRP2 expression is associated with low Breslow thickness and low clinical stage in primary melanomas. Taken together, the present study describes the characteristics of LRP2-expressing melanoma and reveals interferon-gamma signaling as a novel strong positive regulator of LRP2 expression in melanoma.

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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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