Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes.

Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes.
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DOI:
10.1186/s12943-017-0730-8
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发表时间:
2017-10-13
期刊:
影响因子:
37.3
通讯作者:
Scala G
Scala G
中科院分区:
医学1区
文献类型:
--
作者:
Iaccino E;Mimmi S;Dattilo V;Marino F;Candeloro P;Di Loria A;Marimpietri D;Pisano A;Albano F;Vecchio E;Ceglia S;Golino G;Lupia A;Fiume G;Quinto I;Scala G

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肿瘤源性外泌体(Tumor-derived exosomes,TDEs)在肿瘤的形成和发展中起着关键作用,是个体化医学中肿瘤诊断的新兴生物标志物。迄今为止,缺乏用于外泌体分离和表征的有效技术平台。多发性骨髓瘤(MM)是一种无法治愈的B细胞恶性肿瘤,由于迅速发展的耐药性。MM释放的外泌体表达肿瘤B细胞的免疫球蛋白B细胞受体(Ig-BCR),其可以被特发性结合肽(Id-肽)靶向。在这项研究中,我们分析了在小鼠5 T33 MM多发性骨髓瘤模型中MM释放的外泌体作为肿瘤生长生物标志物的产生。为此,我们通过使用由5 T33 MM细胞表达的Ig-BCR作为诱饵筛选噬菌体展示文库来选择Id-肽。通过FACS,FITC缀合的Id-肽检测到5 T33 MM移植小鼠血清中MM释放的外来体,与血清副蛋白相比,其水平与较早时间点的肿瘤进展相关。这些结果表明,MM释放的外泌体的基于Id肽的识别可能代表用于疾病进展的临床评价的非常敏感的诊断方法。本文的在线版本(10.1186/s12943-017-0730-8)包含补充材料,可供授权用户使用。
Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression. The online version of this article (10.1186/s12943-017-0730-8) contains supplementary material, which is available to authorized users.
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