肿瘤-类器官系统的微环境增强了肝细胞癌的恶性相关特征。

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Organogenesis Pub Date : 2017-07-03 Epub Date: 2017-05-26 DOI:10.1080/15476278.2017.1322243
Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu
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引用次数: 20

摘要

类器官微环境和三维(3D)细胞培养构象被认为是在微观尺度上模拟整个器官细胞功能和体内相互作用的有前途的方法。我们使用这种方法来检查肝细胞癌(HCC)细胞的生物学特征。在这项研究中,我们证明肝细胞癌(HCC)细胞、成纤维细胞、内皮细胞和细胞外基质可以产生类器官样球体,这些球体增强了体内观察到的人类HCC的许多特征。我们发现非实质细胞如成纤维细胞和内皮细胞的加入是球体形成和维持组织样结构所必需的。此外,与仅含HCC细胞的类器官相比,非实质细胞球形培养的HCC细胞表达更多的新血管生成相关标志物(VEGFR2、VEGF、HIF-α)、肿瘤相关炎症因子(CXCR4、CXCL12、TNF-α)和诱导上皮-间质转化相关分子(TGFβ、Vimentin、MMP9)。这些结果表明非实质细胞在肝细胞癌类器官的细胞组成中的重要性。基于多细胞的器官型培养系统的新颖性有力地支持了该方法在高通量方法中的整合,以识别患者特异性HCC恶性肿瘤和手术后准确的抗肿瘤治疗筛查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks.

Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks.

Organ-like microenviroment and 3-dimensional (3D) cell culture conformations have been suggested as promising approaches to mimic in a micro-scale a whole organ cellular functions and interactions present in vivo. We have used this approach to examine biologic features of hepatocellular carcinoma (HCC) cells. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo. We show that the addition of non-parenchymal cells such as fibroblast and endothelial cells is required for spheroid formation as well as the maintenance of the tissue-like structure. Furthermore, HCC cells cultured as spheroids with non-parenchymal cells express more neo-angiogenesis-related markers (VEGFR2, VEGF, HIF-α), tumor-related inflammatory factors (CXCR4, CXCL12, TNF-α) and molecules-related to induced epithelial-mesenchymal transition (TGFβ, Vimentin, MMP9) compared with organoids containing only HCC cells. These results demonstrate the importance of non-parenchymal cells in the cellular composition of HCC organoids. The novelty of the multicellular-based organotypic culture system strongly supports the integration of this approach in a high throughput approach to identified patient-specific HCC malignancy and accurate anti-tumor therapy screening after surgery.

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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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