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用于研究肿瘤转移的脱细胞和细胞肺模型。

Acellular and Cellular Lung Model to Study Tumor Metastasis.

作者信息

Mishra Dhruva K, Kim Min P

机构信息

Department of Surgery, Houston Methodist Hospital Research Institute.

Department of Surgery, Houston Methodist Hospital Research Institute; Division of Thoracic Surgery, Department of Surgery, Weill Cornell Medical College, Houston Methodist Hospital;

出版信息

J Vis Exp. 2018 Aug 19(138):58145. doi: 10.3791/58145.

DOI:10.3791/58145
PMID:30176007
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6128209/
Abstract

It is difficult to isolate tumor cells at different points of tumor progression. We created an ex vivo lung model that can show the interaction of tumor cells with a natural matrix and continual flow of nutrients, as well as a model that shows the interaction of tumor cells with normal cellular components and a natural matrix. The acellular ex vivo lung model is created by isolating a rat heart-lung block and removing all the cells using the decellularization process. The right main bronchus is tied off and tumor cells are placed in the trachea by a syringe. The cells move and populate the left lung. The lung is then placed in a bioreactor where the pulmonary artery receives a continual flow of media in a closed circuit. The tumor grown on the left lung is the primary tumor. The tumor cells that are isolated in the circulating media are circulating tumor cells and the tumor cells in the right lung are metastatic lesions. The cellular ex vivo lung model is created by skipping the decellularization process. Each model can be used to answer different research questions.

摘要

在肿瘤进展的不同阶段分离肿瘤细胞是困难的。我们创建了一个离体肺模型,它可以展示肿瘤细胞与天然基质的相互作用以及营养物质的持续流动,还创建了一个展示肿瘤细胞与正常细胞成分和天然基质相互作用的模型。无细胞离体肺模型是通过分离大鼠心肺块并使用脱细胞过程去除所有细胞而创建的。右主支气管被结扎,肿瘤细胞通过注射器注入气管。细胞移动并在左肺中聚集。然后将肺置于生物反应器中,肺动脉在封闭回路中接受持续的培养基流动。在左肺上生长的肿瘤是原发性肿瘤。在循环培养基中分离出的肿瘤细胞是循环肿瘤细胞,右肺中的肿瘤细胞是转移病灶。细胞离体肺模型是通过跳过脱细胞过程而创建的。每个模型都可用于回答不同的研究问题。

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本文引用的文献

1
Small cell and non small cell lung cancer form metastasis on cellular 4D lung model.小细胞肺癌和非小细胞肺癌在 4D 肺部细胞模型中形成转移。
BMC Cancer. 2018 Apr 18;18(1):441. doi: 10.1186/s12885-018-4358-x.
2
Circulating tumor cells and CDX models as a tool for preclinical drug development.循环肿瘤细胞和CDX模型作为临床前药物开发的工具。
Transl Lung Cancer Res. 2017 Aug;6(4):397-408. doi: 10.21037/tlcr.2017.08.01.
3
Breast cancer cells form primary tumors on ex vivo four-dimensional lung model.乳腺癌细胞在体外四维肺模型上形成原发性肿瘤。
J Surg Res. 2017 Apr;210:181-187. doi: 10.1016/j.jss.2016.11.019. Epub 2016 Nov 17.
4
Cancer Statistics, 2017.《2017 年癌症统计》
CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
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Lung Cancer Statistics.肺癌统计数据。
Adv Exp Med Biol. 2016;893:1-19. doi: 10.1007/978-3-319-24223-1_1.
6
Human Lung Fibroblasts Inhibit Non-Small Cell Lung Cancer Metastasis in Ex Vivo 4D Model.人肺成纤维细胞在体外4D模型中抑制非小细胞肺癌转移
Ann Thorac Surg. 2015 Oct;100(4):1167-74; discussion 1174. doi: 10.1016/j.athoracsur.2015.05.014. Epub 2015 Jul 30.
7
Ex vivo four-dimensional lung cancer model mimics metastasis.体外四维肺癌模型模拟转移。
Ann Thorac Surg. 2015 Apr;99(4):1149-56. doi: 10.1016/j.athoracsur.2014.08.085. Epub 2015 Feb 18.
8
Circulating tumor cells from a 4-dimensional lung cancer model are resistant to cisplatin.来自四维肺癌模型的循环肿瘤细胞对顺铂耐药。
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Gene expression profile of A549 cells from tissue of 4D model predicts poor prognosis in lung cancer patients.4D 模型组织中 A549 细胞的基因表达谱预测肺癌患者预后不良。
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Human lung cancer cells grown in an ex vivo 3D lung model produce matrix metalloproteinases not produced in 2D culture.在体外 3D 肺模型中生长的人肺癌细胞产生基质金属蛋白酶,而在 2D 培养中不产生这些酶。
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