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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Opposite roles of metastasin (S100A4) in two potentially tumoricidal mechanisms involving human lymphocyte protein Tag7 and Hsp70
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Opposite roles of metastasin (S100A4) in two potentially tumoricidal mechanisms involving human lymphocyte protein Tag7 and Hsp70

机译：Metastasin（S100A4）在涉及人类淋巴细胞蛋白Tag7和Hsp70的两种潜在的肿瘤机制中的相反作用

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摘要

We compare the physical and functional interactions between three widespread multifunctional proteins [metastasin (Mts1/ S100A4), innate immunity-related Tag7/PGRP-5, and Hsp70] in two experimental models relevant to host-tumor relationships on humoral and cellular levels. (ⅰ) Tag7 and Hsp70 in solution or in a lymphocyte make a stable binary complex that is highly cyto-toxic for some tumor cells. Here, we show that Mts1 prevents Tag7Hsp70 assembly in solution, and an excess of Mts1 disrupts the existing Tag7Hsp70 complex; accordingly, Tag7·Hsp70 cyto-toxicity (exemplified with L929 cells) is diminished in the presence of excess Mts1. (ⅱ) Tag7 exposed on a specialized subset of lymphokine-activated killer cells makes specific contact with Hsp70 exposed on some HLA-negative tumor cells, thus enabling FasL/ Fas-mediated induction of apoptosis. Here, we show that some CD4~+CD25~+ cells coexpose Mts1 with Tag7 and FasL, that Mts1 and Tag7 closely contact the same Hsp70 molecule on the target K562 cell (as evidenced by cross-linking), and that killing of such targets is abolished by Mts1-specific antibodies (or selective removal of Mts1-exposing lymphocytes). Thus, this phenotype active against immunoevasive cancerous cells is defined as CD4~+CD25~+, FasL~+, Tag7~+Mts1~+ (≈0.5% of total lymphocytes in culture). Remarkably, similar effectors with at least the same activity are often found in fresh donor blood samples ( ≈10~4 effectors/mL). Thus, our models suggest that interactions between the three proteins in different situations may have opposite functional outcomes as regards antitumor defense, immune escape, and metastasis.
机译：我们在两个与体液和细胞水平上的宿主-肿瘤关系相关的实验模型中比较了三种广泛的多功能蛋白[metastasin（Mts1 / S100A4），与先天性免疫相关的Tag7 / PGRP-5和Hsp70]之间的物理和功能相互作用。 （ⅰ）溶液或淋巴细胞中的Tag7和Hsp70形成稳定的二元复合物，对某​​些肿瘤细胞具有高度的细胞毒性。在这里，我们展示了Mts1阻止了解决方案中的Tag7Hsp70组装，而过多的Mts1破坏了现有的Tag7Hsp70复合体。因此，在过量的Mts1存在下，Tag7·Hsp70的细胞毒性（以L929细胞为例）减少了。 （ⅱ）暴露于淋巴因子激活的杀伤细胞特定亚群的Tag7与暴露于某些HLA阴性肿瘤细胞上的Hsp70发生特异性接触，从而实现FasL / Fas介导的凋亡诱导。在这里，我们发现一些CD4〜+ CD25〜+细胞与Mts1与Tag7和FasL共同暴露，Mts1和Tag7紧密接触靶K562细胞上的同一Hsp70分子（通过交联证明），并且杀死了这些靶Mts1特异性抗体（或选择性去除Mts1暴露的淋巴细胞）消除了这种作用。因此，这种对免疫逃避性癌细胞有效的表型被定义为CD4〜+ CD25〜+，FasL〜+，Tag7〜+ Mts1〜+（约占培养物中总淋巴细胞的0.5％）。值得注意的是，在新鲜的供体血液样本中经常发现具有至少相同活性的相似效应子（≈10〜4个效应子/ mL）。因此，我们的模型表明三种蛋白质在不同情况下的相互作用在抗肿瘤防御，免疫逃逸和转移方面可能具有相反的功能结果。

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    Elena A. Dukhanina; Olga D. Kabanova; Tamara I. Lukyanova; Yury V. Shatalov; Denis V. Yashin; Elena A. Romanova; Nikolai V. Gnuchev; Alexander V. Galkin; Georgii P. Georgiev; Lidia P. Sashchenko;

  • 作者单位

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia Laboratory of Nucleic Acids Biosynthesis, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia Centre for Medical Studies in Russia, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

    Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences, University of Oslo, 34/5 Vavilova Street, Moscow 119334, Russia;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    immune responses to cancer; metastasis;

    机译：对癌症的免疫反应;转移;

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