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不同的外泌体分泌模式是患者来源的结直肠癌多细胞球体及其小鼠异种移植瘤的特征。

A Different Exosome Secretion Pattern Characterizes Patient-Derived Colorectal Cancer Multicellular Spheroids and Their Mouse Xenografts.

作者信息

Relucenti Michela, Francescangeli Federica, De Angelis Maria Laura, D'Andrea Vito, Miglietta Selenia, Donfrancesco Orlando, Li Xiaobo, Chen Rui, Zeuner Ann, Familiari Giuseppe

机构信息

Section of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy.

Department of Oncology and Molecular Medicine, National Institute of Health (Istituto Superiore di Sanità), 00161 Rome, Italy.

出版信息

Biology (Basel). 2022 Sep 29;11(10):1427. doi: 10.3390/biology11101427.

DOI:10.3390/biology11101427
PMID:36290331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9599039/
Abstract

Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancer lineage responsible for CRC and its metastatic behavior and responsiveness to therapy are needed. Exosomes' role in tumorigenesis and the metastatic process was demonstrated, and the material content and size of the exosomes are associated with a poor prognosis of CRC. Exosomes are generally imagined after their recovery from blood serum as isolated entities, and our work aims to investigate them "in situ" in their native environment by scanning and transmission electron microscopy to understand their secretion modalities. We studied CRC stem cells in patient-derived multicellular tumor spheroids (MTSs) and in their mouse xenograft to find possible differences in terms of exosome amount, size, and secretion site between in vitro and in vivo models. We observed that MTSs' exosome secretion patterns depend on their structural complexity: few-layer MTSs show a lesser exosome secretion, limited to the apical domain of cancer cells, secretion increases in multilayered MTSs, and it develops from apical and basolateral cancer cells domains. In xenograft models, exosome secretion occurs from all cancer cell domains, and it is quantitatively greater than that observed in MTSs. This difference in exosome secretion pattern between MTSs and xenografts may be due to the influence of surrounding non-tumor cells.

摘要

需要有最新的体外和体内临床前模型，这些模型要能表达导致结直肠癌及其转移行为和对治疗反应的患者特异性癌症谱系。已证实外泌体在肿瘤发生和转移过程中的作用，并且外泌体的物质含量和大小与结直肠癌的不良预后相关。外泌体通常是在从血清中分离出来后才被视作独立的实体，而我们的工作旨在通过扫描电子显微镜和透射电子显微镜在其天然环境中“原位”研究它们，以了解其分泌方式。我们研究了源自患者的多细胞肿瘤球状体（MTS）及其小鼠异种移植模型中的结直肠癌干细胞，以找出体外和体内模型在外泌体数量、大小和分泌部位方面可能存在的差异。我们观察到，MTS的外泌体分泌模式取决于其结构复杂性：单层MTS的外泌体分泌较少，仅限于癌细胞的顶端区域，多层MTS的分泌增加，且从顶端和基底外侧癌细胞区域分泌。在异种移植模型中，外泌体从所有癌细胞区域分泌，并且在数量上比在MTS中观察到的更多。MTS和异种移植在外泌体分泌模式上的这种差异可能是由于周围非肿瘤细胞的影响。

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本文引用的文献

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Role of exosomes in cellular communication between tumor cells and the tumor microenvironment.外泌体在肿瘤细胞与肿瘤微环境之间细胞通讯中的作用。
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Chemotherapeutic Risk lncRNA-PVT1 SNP Sensitizes Metastatic Colorectal Cancer to FOLFOX Regimen.
成人异柠檬酸脱氢酶野生型胶质母细胞瘤的超微结构研究表明形态学生物标志物与Ki-67指数之间可能存在相关性。
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化疗风险长链非编码RNA-PVT1单核苷酸多态性使转移性结直肠癌对FOLFOX方案敏感。
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The Role of Tumor Stem Cell Exosomes in Cancer Invasion and Metastasis.肿瘤干细胞外泌体在癌症侵袭和转移中的作用
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Colorectal Cancer Stem Cells: An Overview of Evolving Methods and Concepts.结直肠癌干细胞：不断发展的方法与概念概述
Cancers (Basel). 2021 Nov 24;13(23):5910. doi: 10.3390/cancers13235910.
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The Ultrastructural Analysis of Human Colorectal Cancer Stem Cell-Derived Spheroids and Their Mouse Xenograft Shows That the Same Cells Types Have Different Ratios.人结直肠癌干细胞来源的球体及其小鼠异种移植的超微结构分析表明，相同细胞类型具有不同比例。
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