具有明确突变的新型小鼠细胞系可模拟上皮性卵巢癌的不同组织学亚型。

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2025-07-01 Epub Date: 2025-07-28 DOI:10.1242/dmm.052177
Lixin Zhang, Yusi Fang, Ibrahim Uygun, Danyang Li, Mary Strange, Syed K Zaidi, Wenjia Wang, Julia Knight, Mackenzy Radolec, Esther Elishaev, Joan F Brozick, Allison Edwards, George Tseng, Sandra Cascio, Ronald Buckanovich, Robert P Edwards, Anda M Vlad
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引用次数: 0

摘要

在免疫功能正常的小鼠中,上皮性卵巢癌进展为原位自发肿瘤的临床前模型具有挑战性,需要在宿主中进行多次遗传修饰。使用细胞系的可移植模型更容易实现,因为它们可以复制关键的疾病特征。为了建立新的体内卵巢肿瘤模型,我们共生成了28株具有不同遗传性状的小鼠卵巢癌细胞系,如缺失Trp53、激活KrasG12D、缺失Pten或KrasG12D/Pten-/-组合。两种不同的Trp53零细胞系在免疫能力强的同基因宿主中原位注射时重现高级别浆液组织学。Pten缺失的细胞触发高级别子宫内膜样肿瘤,KrasG12D双激活和Pten缺失的细胞模型癌肉瘤。这些细胞表达不同的肿瘤抗原,分泌不同水平的细胞因子和趋化因子,并引发具有不同炎症特征和不同肿瘤内T和B淋巴细胞浸润模式的肿瘤。来自16个细胞系的RNAseq数据揭示了不同组织类型的不同模型的基因表达谱。这个多功能的小鼠细胞系集合支持卵巢癌翻译相关的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Murine cell lines with defined mutations model different histological subtypes of epithelial ovarian cancer.

Preclinical modeling of epithelial ovarian cancer in immune-competent mice progressing to orthotopic, spontaneous tumors is challenging, requiring multiple genetic modifications in the host. Transplantable models using cell lines are easier to implement than spontaneous animal models, given that they reproduce the key disease characteristics. To create new in vivo ovarian tumor models, we generated 28 murine ovarian cancer cell lines with distinct genetic traits, such as deletion of Trp53, activation of KrasG12D, or deletion of Pten or KrasG12D/Pten-/- combination. Two distinct Trp53 null cell lines recapitulate high-grade serous histology when orthotopically injected into immune-competent, syngeneic hosts. Cells with Pten deletion trigger high-grade endometrioid tumors, and cells with dual KrasG12D activation and Pten deletion model carcinosarcoma. The cells express different tumor antigens, secrete varying levels of cytokines and chemokines, and trigger tumors with diverse inflammation profiles and various intratumoral T- and B-lymphocyte infiltration patterns. RNA-sequencing data from 16 cell lines reveal the gene expression profile across distinct models with different histotypes. This versatile collection of murine cell lines supports translationally relevant studies in ovarian cancer.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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