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人类三阴性乳腺癌类器官培养可靠方法的开发：改进三维培养中的成像和基因组研究。

Development of a reliable method for human triple-negative breast cancer organotypic culture: Improving imaging and genomic studies in 3D cultures.

作者信息

Olvera-Valencia Mercedes, Garcia-Castillo Verónica, Ramos-Payan Rosalío, Aguilar-Medina Maribel, Trujano-Camacho Samuel, López-Saavedra Alejandro, Marchat Laurence A, López-Camarillo Cesar, Sumagin Ronen, Pérez-Yepez Eloy, Pérez-Plasencia Carlos

机构信息

Programa Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ticoman, CDMX, Mexico.

Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, CDMX, Mexico.

出版信息

J Tissue Eng. 2025 May 7;16:20417314251326668. doi: 10.1177/20417314251326668. eCollection 2025 Jan-Dec.

DOI:10.1177/20417314251326668
PMID:40342587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12059422/
Abstract

Triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies, posing a major challenge in oncology. Traditional two-dimensional (2D) cell cultures fail to capture the tumor microenvironment's complexity, whereas three-dimensional (3D) cultures provide a more accurate model of tumor biology. We developed an advanced 3D culture system for TNBC cell lines BT-20 and MDA-MB-231, enhancing the hanging-drop method with Matrigel to restore essential extracellular matrix interactions. Confocal imaging showed MDA-MB-231 cells forming clusters typical of aggressive carcinoma, while BT-20 cells organized into duct-like structures. Molecular analysis of PI3K and β-catenin target genes revealed distinct expression patterns, with PI3K overexpressed and β-catenin downregulated in 3D cultures. Moreover, β-catenin distribution in the 3D cell culture closely resembles its pattern in tissue. These findings underscore the value of 3D models in understanding TNBC progression and in supporting the exploration of novel therapeutic strategies.

摘要

三阴性乳腺癌（TNBC）具有高度侵袭性且缺乏靶向治疗方法，这在肿瘤学领域构成了一项重大挑战。传统的二维（2D）细胞培养无法体现肿瘤微环境的复杂性，而三维（3D）培养则提供了更精确的肿瘤生物学模型。我们为TNBC细胞系BT - 20和MDA - MB - 231开发了一种先进的3D培养系统，通过基质胶改进悬滴法以恢复关键的细胞外基质相互作用。共聚焦成像显示，MDA - MB - 231细胞形成了侵袭性癌典型的细胞簇，而BT - 20细胞则组织成导管样结构。对PI3K和β-连环蛋白靶基因的分子分析揭示了不同的表达模式，在3D培养中PI3K过表达而β-连环蛋白下调。此外，β-连环蛋白在3D细胞培养中的分布与它在组织中的模式非常相似。这些发现凸显了3D模型在理解TNBC进展以及支持新型治疗策略探索方面的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/22e20fb7116f/10.1177_20417314251326668-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/88deb48298cd/10.1177_20417314251326668-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/bcb0f314e223/10.1177_20417314251326668-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/c847c59582e0/10.1177_20417314251326668-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/2c3485fdbbfe/10.1177_20417314251326668-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/22e20fb7116f/10.1177_20417314251326668-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/88deb48298cd/10.1177_20417314251326668-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/bcb0f314e223/10.1177_20417314251326668-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/c847c59582e0/10.1177_20417314251326668-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/2c3485fdbbfe/10.1177_20417314251326668-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1505/12059422/22e20fb7116f/10.1177_20417314251326668-fig5.jpg

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Scaffold-based 3D cell culture models in cancer research.
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