Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu
{"title":"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。","authors":"Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu","doi":"10.1080/15476278.2017.1322243","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"13 3","pages":"83-94"},"PeriodicalIF":1.6000,"publicationDate":"2017-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2017.1322243","citationCount":"20","resultStr":"{\"title\":\"Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks.\",\"authors\":\"Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu\",\"doi\":\"10.1080/15476278.2017.1322243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":19596,\"journal\":{\"name\":\"Organogenesis\",\"volume\":\"13 3\",\"pages\":\"83-94\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2017-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/15476278.2017.1322243\",\"citationCount\":\"20\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organogenesis\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1080/15476278.2017.1322243\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/5/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organogenesis","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1080/15476278.2017.1322243","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/5/26 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.