Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.

IF 4.5 2区 医学 Q1 ONCOLOGY
Translational Oncology Pub Date : 2025-02-01 Epub Date: 2025-01-13 DOI:10.1016/j.tranon.2024.102269
Sharada Mokkapati, Ganiraju Manyam, Alexis R Steinmetz, Côme Tholomier, Alberto Martini, Woonyoung Choi, Bogdon Czerniak, Byron H Lee, Colin P Dinney, David J McConkey
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引用次数: 0

Abstract

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models. Patient-derived, luciferase-tagged BLCA cell lines were cultured in vitro and engrafted into bladders of NSG mice. Tumor growth was monitored using bioluminescence imaging and mRNA-based molecular classification was used to characterize xenografts into molecular subtypes. RNAseq analysis and basal, luminal, and epithelial-mesenchymal transition (EMT) marker expression revealed distinct patterns; certain cell lines expressed predominantly basal or luminal markers while others demonstrated mixed expression. SCaBER expressed high basal and EMT markers and low luminal markers, consistent with a true basal cell. RT4V6 was a true luminal cell line, displaying only high luminal makers. UC13, T24 and UC3 only showed increased expression of EMT markers. RT112, UC6, UC9 and UC14 expressed basal, luminal, and EMT markers. Immunohistochemical analysis validated our findings. Ki67 was assessed as a continuous percentage of positively stained cells. Morphological assessment of xenografts included H&E and α-SMA staining. These findings will allow for the rational use of appropriate models to develop targeted therapies to overcome or manipulate mechanisms of treatment resistance in BLCA.

膀胱癌异种移植物的分子图谱分析确定了相关的分子亚型,并为生物标记物的发现提供了资源。
膀胱癌(BLCA)基因组分析已经确定了具有不同临床特征和对一线治疗敏感性的分子亚型。根据基因表达的不同,blca可分为管状亚型和基底亚型。我们利用同种异种移植模型对9种人BLCA细胞系(UC3、UC6、UC9、UC13、UC14、T24、scer、RT4V6和RT112)进行了分子亚型的全面表征。患者来源的荧光素酶标记的BLCA细胞系在体外培养并移植到NSG小鼠的膀胱中。利用生物发光成像监测肿瘤生长,并利用基于mrna的分子分类将异种移植物划分为分子亚型。RNAseq分析和基底、腔内和上皮-间质转化(EMT)标记的表达显示出不同的模式;某些细胞系主要表达基底或腔内标记物,而其他细胞系则表现出混合表达。scer表达高基底和EMT标记物和低腔标记物,与真正的基底细胞一致。RT4V6是一个真正的荧光细胞系,只显示高荧光细胞。UC13、T24和UC3仅显示EMT标记物表达增加。RT112、UC6、UC9和UC14表达基础、luminal和EMT标记物。免疫组织化学分析证实了我们的发现。Ki67以阳性染色细胞的连续百分比进行评估。形态学评价采用H&E染色和α-SMA染色。这些发现将允许合理使用适当的模型来开发靶向治疗,以克服或操纵BLCA的治疗耐药机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Translational Oncology
Translational Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
7.20
自引率
2.00%
发文量
314
审稿时长
6-12 weeks
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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