在小鼠乳腺上皮细胞中,FBLN2 与基底细胞标志物 Krt14 和 ITGB1 相关,并在人类乳腺癌分子亚型中优先表达。

IF 3 3区 医学 Q2 ONCOLOGY Breast Cancer Research and Treatment Pub Date : 2024-12-01 Epub Date: 2024-08-07 DOI:10.1007/s10549-024-07447-y
Amr Ahmed WalyEldeen, Salwa Sabet, Shady E Anis, Torsten Stein, Ayman M Ibrahim
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引用次数: 0

摘要

背景:Fibulin-2(FBLN2)是一种分泌型细胞外基质(ECM)糖蛋白,已在小鼠乳腺、青春期终末芽(TEB)的帽细胞和妊娠早期肌上皮细胞周围被发现。乳腺上皮基底膜(BM)的完整性需要它,它的缺失与人类乳腺癌的侵袭有关。在此,我们试图证实FBLN2与乳腺上皮细胞肌上皮表型的相关性,并评估其在人类乳腺癌分子亚型中的表达情况:方法:采用免疫组织化学、免疫细胞化学和免疫印迹法研究了青春期小鼠乳腺和EpH4小鼠乳腺上皮细胞系中FBLN2的表达与上皮标记物之间的关系。分析了来自生物门户网站 METABRIC 和 TCGA 数据集的人类乳腺癌 mRNA 数据,以评估 Fbln2 表达与上皮标志物以及分子亚型的关联。利用METABRIC数据集和KM数据库的数据生成了生存曲线:结果:在小鼠乳腺上皮细胞中敲除 FBLN2 与 KRT14 的减少和 KRT18 的增加有关。此外,TGFβ3处理导致体外FBLN2上调。对来自Bioportal的人类乳腺癌数据集进行的元分析表明,与LumB、Her2 +和基底样亚组相比,低Claudin、LumA和正常样乳腺癌中Fbln2 mRNA的表达量更高。Fbln2 mRNA水平与间质标志物、肌上皮标志物以及上皮-间质转化标志物呈正相关。在晚期乳腺癌中,Fbln2 mRNA的高表达与较好的预后有关,而在晚期病变中,这种模式发生了逆转:结论:随着进一步的验证,这些观察结果可能会为人类乳腺癌的分子预后提供一种工具,从而为更个性化的治疗方法提供依据。
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FBLN2 is associated with basal cell markers Krt14 and ITGB1 in mouse mammary epithelial cells and has a preferential expression in molecular subtypes of human breast cancer.

Background: Fibulin-2 (FBLN2) is a secreted extracellular matrix (ECM) glycoprotein and has been identified in the mouse mammary gland, in cap cells of terminal end buds (TEBs) during puberty, and around myoepithelial cells during early pregnancy. It is required for basement membrane (BM) integrity in mammary epithelium, and its loss has been associated with human breast cancer invasion. Herein, we attempted to confirm the relevance of FBLN2 to myoepithelial phenotype in mammary epithelium and to assess its expression in molecular subtypes of human breast cancer.

Methods: The relationship between FBLN2 expression and epithelial markers was investigated in pubertal mouse mammary glands and the EpH4 mouse mammary epithelial cell line using immunohistochemistry, immunocytochemistry, and immunoblotting. Human breast cancer mRNA data from the METABRIC and TCGA datasets from Bioportal were analyzed to assess the association of Fbln2 expression with epithelial markers, and with molecular subtypes. Survival curves were generated using data from the METABRIC dataset and the KM databases.

Results: FBLN2 knockdown in mouse mammary epithelial cells was associated with a reduction in KRT14 and an increase in KRT18. Further, TGFβ3 treatment resulted in the upregulation of FBLN2 in vitro. Meta-analyses of human breast cancer datasets from Bioportal showed a higher expression of Fbln2 mRNA in claudin-low, LumA, and normal-like breast cancers compared to LumB, Her2 +, and Basal-like subgroups. Fbln2 mRNA levels were positively associated with mesenchymal markers, myoepithelial markers, and markers of epithelial-mesenchymal transition. Higher expression of Fbln2 mRNA was associated with better prognosis in less advanced breast cancer and this pattern was reversed in more advanced lesions.

Conclusion: With further validation, these observations may offer a molecular prognostic tool for human breast cancer for more personalized therapeutic approaches.

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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
342
审稿时长
1 months
期刊介绍: Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.
期刊最新文献
Correction: FBLN2 is associated with basal cell markers Krt14 and ITGB1 in mouse mammary epithelial cells and has a preferential expression in molecular subtypes of human breast cancer. A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer. Alterations in the expression of homologous recombination repair (HRR) genes in breast cancer tissues considering germline BRCA1/2 mutation status. Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors. Cost containment analysis of superparamagnetic iron oxide (SPIO) injection in patients with ductal carcinoma in situ.
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