Background/Objectives: Conventional two-dimensional (2D) cell cultures offer valuable insights into cancer cell biology; however, they lack in replicating the complex interactions present in solid tumors. Therefore, research has shifted towards the development of three-dimensional (3D) cell models that recapitulate the dynamic cell–cell and cell–matrix interactions within the complex tumor microenvironment (TME), better resembling tumor growth and initial stages of dissemination. Extracellular matrix, a key component within the TME, regulates cell morphology and signaling, influencing key functional properties. Breast cancer remains the most frequently diagnosed cancer type in women and a leading cause of cancer-related mortality.Methods: The aim of the present study was the development of breast cancer cell-derived spheroids, utilizing two breast cancer cell lines with differential estrogen receptor (ER) expression profile, and their characterization in terms of morphology, functional properties, and expression of epithelial-to-mesenchymal transition (EMT) markers and matrix signatures implicated in breast cancer progression. To this end, the ERα-positive MCF-7, and ERβ-positive MDA-MB-231 breast cancer cell lines were utilized.Results: Our findings revealed notable phenotypic transitions between 2D and 3D cultures, which were further supported by differential EMT markers expression. Moreover, spheroids exhibited distinct expression profiles of key receptors [ERs, epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGF1R)] and matrix molecules (syndecans, and matrix metalloproteinases), accompanied by altered functional cell properties. Bioinformatic tools further emphasized the interplay between the studied matrix regulators and their prognostic relevance in breast cancer.Conclusions: Overall, this study introduces a simple yet informative 3D breast cancer model that captures key TME features to better predict cell behavior in vitro.
背景/目的：传统的二维细胞培养为癌细胞生物学提供了重要见解，但其无法复现实体肿瘤中存在的复杂相互作用。因此，研究已转向开发三维细胞模型，该模型能重现复杂肿瘤微环境中的动态细胞-细胞及细胞-基质相互作用，从而更准确地模拟肿瘤生长及早期扩散阶段。细胞外基质作为肿瘤微环境的关键组分，通过调控细胞形态与信号传导影响细胞的核心功能特性。乳腺癌仍是女性最常见的癌症类型，也是癌症相关死亡的主要原因。 方法：本研究旨在利用两种雌激素受体表达谱不同的乳腺癌细胞系，建立乳腺癌细胞来源的球体模型，并从形态学、功能特性、上皮-间质转化标志物表达以及与乳腺癌进展相关的基质特征等方面对其进行表征。为此，本研究采用了ERα阳性的MCF-7细胞系和ERβ阳性的MDA-MB-231乳腺癌细胞系。 结果：研究发现二维与三维培养体系间存在显著的表型差异，这一现象通过差异化的上皮-间质转化标志物表达得到进一步验证。此外，球体模型在关键受体（雌激素受体、表皮生长因子受体和胰岛素样生长因子受体）及基质分子（多配体蛋白聚糖和基质金属蛋白酶）的表达谱上呈现显著特征，并伴随细胞功能特性的改变。生物信息学工具进一步揭示了所研究的基质调控因子之间的相互作用及其在乳腺癌中的预后相关性。 结论：本研究构建了一种简洁而信息丰富的三维乳腺癌模型，该模型能够捕捉肿瘤微环境的关键特征，从而更有效地预测体外细胞行为。
Spheroid-Based 3D Models to Decode Cell Function and Matrix Effectors in Breast Cancer
肿瘤(癌症)患者之家