Comparative Glycoproteomic Analysis of Mouse 4T1 Breast Cancer Model.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aik-Aun Tan, Yin-Ling Wong, Subash C B Gopinath, Lik Voon Kiew, Sreenivasan Sasidharan, Yeng Chen
{"title":"Comparative Glycoproteomic Analysis of Mouse 4T1 Breast Cancer Model.","authors":"Aik-Aun Tan, Yin-Ling Wong, Subash C B Gopinath, Lik Voon Kiew, Sreenivasan Sasidharan, Yeng Chen","doi":"10.2174/0109298673360978250329065548","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Glycosylation is a post-translational modification process that plays a fundamental role in malignant transformation. Moreover, aberrant glycosylation is known to be associated with cancer progression. Thus, the characterization of cancer-specific protein glycosylation profiles might reveal important diagnostic and/or prognostic biomarkers for cancer.</p><p><strong>Objective: </strong>In the present study, we have analysed serum protein and glycoprotein profiles during breast cancer progression using a mouse model. Specifically, 4T1 tumour cells were injected into the mammary fat pad of BALB/c mice to induce tumours.</p><p><strong>Methods: </strong>Sera samples were subsequently collected weekly for four weeks and examined using two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis, followed by mass spectrometry.</p><p><strong>Results: </strong>This glycoproteomic profiling identified eight differentially expressed proteins, of which alpha-1 protease inhibitor 2, contraption (CON), haptoglobin (HP), and kininogen-1 were significantly up-regulated during the first 4 weeks of tumour progression. Notably, aberrantly N-glycosylated prothrombin was also detected in sera samples from all mice over the 4 weeks post-tumour injection. Additionally, O-glycosylated alpha-2-macroglobulin, CON, and HP were detected in weeks 1 and 2, whereas O-glycosylated alpha-2-HS-glycoprotein and CON were detected on weeks 3 and 4 post-implantation.</p><p><strong>Conclusion: </strong>Our findings indicate that the combination of 2D-E with lectin-based chromatography represents an effective approach for identifying prognostic biomarkers for breast cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0109298673360978250329065548","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Glycosylation is a post-translational modification process that plays a fundamental role in malignant transformation. Moreover, aberrant glycosylation is known to be associated with cancer progression. Thus, the characterization of cancer-specific protein glycosylation profiles might reveal important diagnostic and/or prognostic biomarkers for cancer.

Objective: In the present study, we have analysed serum protein and glycoprotein profiles during breast cancer progression using a mouse model. Specifically, 4T1 tumour cells were injected into the mammary fat pad of BALB/c mice to induce tumours.

Methods: Sera samples were subsequently collected weekly for four weeks and examined using two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis, followed by mass spectrometry.

Results: This glycoproteomic profiling identified eight differentially expressed proteins, of which alpha-1 protease inhibitor 2, contraption (CON), haptoglobin (HP), and kininogen-1 were significantly up-regulated during the first 4 weeks of tumour progression. Notably, aberrantly N-glycosylated prothrombin was also detected in sera samples from all mice over the 4 weeks post-tumour injection. Additionally, O-glycosylated alpha-2-macroglobulin, CON, and HP were detected in weeks 1 and 2, whereas O-glycosylated alpha-2-HS-glycoprotein and CON were detected on weeks 3 and 4 post-implantation.

Conclusion: Our findings indicate that the combination of 2D-E with lectin-based chromatography represents an effective approach for identifying prognostic biomarkers for breast cancer.

小鼠4T1乳腺癌模型糖蛋白组学比较分析。
背景:糖基化是一个翻译后修饰过程,在恶性转化中起着重要作用。此外,已知异常糖基化与癌症进展有关。因此,癌症特异性蛋白糖基化谱的表征可能揭示癌症诊断和/或预后的重要生物标志物。目的:在本研究中,我们利用小鼠模型分析了乳腺癌进展过程中的血清蛋白和糖蛋白谱。具体而言,将4T1肿瘤细胞注射到BALB/c小鼠乳腺脂肪垫中诱导肿瘤。方法:每周采集血清样本,连续4周,采用二维电泳(2D-E)结合凝集素分析,然后采用质谱法进行检测。结果:该糖蛋白组学分析鉴定了8种差异表达蛋白,其中α -1蛋白酶抑制剂2、contraption (CON)、haptoglobin (HP)和kininogen-1在肿瘤进展的前4周显著上调。值得注意的是,在所有小鼠肿瘤注射后4周的血清样本中也检测到异常的n -糖基化凝血酶原。此外,在植入后第1周和第2周检测o -糖化α -2巨球蛋白、CON和HP,而在植入后第3周和第4周检测o -糖化α -2- hs糖蛋白和CON。结论:我们的研究结果表明,2D-E与基于凝集素的色谱相结合是一种识别乳腺癌预后生物标志物的有效方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信