用于研究BRAF V600E突变体肿瘤发生和靶向治疗的新型微卫星稳定结直肠癌细胞系和类器官模型o17

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-09-03 DOI:10.1016/j.bbrep.2025.102235

Chen Zheng , Xuan Tang , Shuang Wang , Yuxuan Xu , Keyang Jia , Ganglong Gao , Guiying Wei , Gengming Niu , Yiwen Wu , Xiaozhe Qian , Ying Zhu , Dongxi Xiang

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引用次数: 0

摘要

人类癌细胞系是研究肿瘤生物学、致癌发生、分子遗传学、转移和肿瘤进化的重要体外模型。在这项研究中，我们建立并鉴定了OT17细胞系，该细胞系来源于中分化至低分化的结直肠癌手术标本。基因分析揭示了OT17的关键突变，包括BRAF V600E、APC和ERBB2，以及TP53的缺失。免疫组织化学分析证实了MLH1、MSH2、MSH6和PMS2的表达，表明微卫星稳定（MSS）表型与原发肿瘤一致。OT17细胞系在体内表现出强大的致瘤性，在NOD-scid Il2rg−/−(NSG)（NSG）小鼠中形成皮下肿瘤的成功率达到100%。此外，建立了相应的3D类器官模型（CO17），该模型与OT17保持遗传一致性，进一步验证了其临床前应用的相关性。总之，o17细胞系和CO17类器官系统代表了推进结直肠癌研究的强大模型，在治疗筛选、免疫疗法开发和MSS肿瘤生物学研究中具有潜在的应用前景。

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OT17 a novel microsatellite stable colorectal cancer cell line and organoid model for investigating BRAF V600E mutant tumorigenesis and targeted therapeutics

Human cancer cell lines serve as essential in vitro models for investigating tumor biology, carcinogenesis, molecular genetics, metastasis, and tumor evolution. In this study, we establish and characterize the OT17 cell line, derived from a moderately to poorly differentiated colorectal adenocarcinoma surgical specimen. Genetic analysis of OT17 revealed key mutations, including BRAF V600E, APC, and ERBB2, along with a deletion in TP53. Immunohistochemical profiling confirmed the expression of MLH1, MSH2, MSH6, and PMS2, indicating a microsatellite-stable (MSS) phenotype consistent with the primary tumor. The OT17 cell line demonstrated robust tumorigenicity in vivo, achieving a 100 % success rate in forming subcutaneous tumors in NOD-scid Il2rg^−/−(NSG)(NSG) mice. Additionally, a corresponding 3D organoid model (CO17) was established, which retained genetic concordance with OT17, further validating its relevance for preclinical applications. Together, the OT17 cell line and CO17 organoid system represent robust models for advancing colorectal cancer research, with potential applications in therapeutic screening, immunotherapy development, and MSS tumor biology studies.

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.