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一对原发性结直肠癌及其相应同步肝转移衍生的类器官细胞系。

A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines.

机构信息

Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, China.

出版信息

Aging (Albany NY). 2024 Feb 24;16(5):4396-4422. doi: 10.18632/aging.205595.

DOI:10.18632/aging.205595
PMID:38407980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10968669/
Abstract

Proper preclinical models for the research of colorectal cancer (CRC) and CRC liver metastases (CLM) are a clear and unmet need. Patient-derived organoids have recently emerged as a robust preclinical model, but are not available to all scientific researchers. Here, we present paired 3D organoid cell lines of CWH22 (CRC-derived) and CLM22 (CLM-derived) with sound background information and the short tandem repeats are identical to those of the normal tissue. Morphological and immunohistochemical staining, along with whole-exome sequencing (WES), confirmed that the organoids exhibited the same differentiation, molecular expression, and mutation status as the corresponding tumor tissue. Both organoids possessed mutated // genes and wild-type and ; stably secreted the tumor markers CEA and CA19-9, and possessed sound proliferation rates , as well as subcutaneous tumorigenicity and liver metastatic abilities . IC assays confirmed that both cell lines were sensitive to 5-fluorouracil, oxaliplatin, SN-38, and sotorasib. WES and karyotype analyses revealed the genomic instability status as chromosome instability. The corresponding adherent cultured CWH22-2D/CLM22-2D cells were established and compared with commonly used CRC cell lines from the ATCC. Both organoids are publicly available to all researchers and will be useful tools for specific human CRC/CLM studies both and

摘要

研究结直肠癌(CRC)和 CRC 肝转移(CLM)的合适临床前模型是明确且未满足的需求。患者来源的类器官最近作为一种强大的临床前模型出现,但并非所有科研人员都能使用。在此,我们提供了配对的 3D 类器官细胞系 CWH22(CRC 衍生)和 CLM22(CLM 衍生),它们具有可靠的背景信息,短串联重复序列与正常组织相同。形态学和免疫组织化学染色以及全外显子组测序(WES)证实,类器官表现出与相应肿瘤组织相同的分化、分子表达和突变状态。两种类器官均携带 // 基因的突变和野生型 // ;稳定分泌肿瘤标志物 CEA 和 CA19-9,并具有良好的增殖率,以及皮下致瘤性和肝转移能力。IC 测定证实两种细胞系均对 5-氟尿嘧啶、奥沙利铂、SN-38 和 sotorasib 敏感。WES 和核型分析显示基因组不稳定性状态为染色体不稳定性。相应的贴壁培养 CWH22-2D/CLM22-2D 细胞被建立并与 ATCC 中常用的 CRC 细胞系进行了比较。两种类器官都可供所有研究人员公开使用,将成为特定人类 CRC/CLM 研究的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0c/10968669/7a1f7c7cd6c7/aging-16-205595-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0c/10968669/75adbdd48e24/aging-16-205595-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0c/10968669/7a1f7c7cd6c7/aging-16-205595-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0c/10968669/81a3650e6544/aging-16-205595-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d0c/10968669/75adbdd48e24/aging-16-205595-g007.jpg
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