Background: Breast cancer, one of the most researched cancers in oncology, remains the primary cause of cancer-related mortality in women. Its biological complexity, which includes phenotypic, genetic, and microenvironmental aspects, makes modeling and treatment quite difficult. The need for more physiologically realistic models is highlighted by the comparison of two-dimensional (2D) cell cultures with 3D breast-cancer-derived spheroids, which discloses how important pathways such as epidermal growth factor receptor (EGFR) and insulin-like growth factor I receptor (IGF-IR) influence cell behavior and extracellular matrix (ECM) macromolecular expression.Methods: The purpose of this study was to utilize novel 3D cell platforms to assess the effect of inhibiting the EGFR and IGF-IR pathways, alone or in combination, on the functional properties and the expression levels of certain matrix metalloproteinases (MMPs) which are implicated in breast cancer progression (i.e., triple-negative and luminal A breast cancer subtypes) and related with the EGFR and IGF-ΙR molecular network, as also demonstrated through STRING analysis.Results: Our results demonstrated potential crosstalk between EGFR and IGF-IR signaling, which influences cell proliferation and spheroid growth, dissemination, and migration. Significant phenotypic changes proposed between 2D and 3D cell cultures, and alterations in the expression of MMPs, were also recorded.Conclusions: Both breast cancer cell lines retained acknowledged characteristics across the tested models while also exhibiting new, condition-dependent properties. Overall, our findings enhance our understanding on the interplay between the EGFR and IGF-IR pathways and underscore the value of 3D models in revealing key biological processes underlying distinct breast cancer phenotypes.
背景：乳腺癌作为肿瘤学领域研究最为深入的癌症之一，仍是女性癌症相关死亡的主要原因。其生物学复杂性涵盖表型、遗传及微环境等多个层面，使得建模与治疗面临巨大挑战。通过对比二维细胞培养与三维乳腺癌来源球体模型，揭示了表皮生长因子受体（EGFR）和胰岛素样生长因子I受体（IGF-IR）等重要通路如何影响细胞行为及细胞外基质大分子表达，这凸显了对更具生理真实性模型的需求。 方法：本研究旨在利用新型三维细胞平台，评估单独或联合抑制EGFR与IGF-IR通路对特定基质金属蛋白酶（MMPs）功能特性及表达水平的影响。这些MMPs与乳腺癌进展（包括三阴性及管腔A型亚型）密切相关，并通过STRING分析证实其与EGFR/IGF-IR分子网络存在关联。 结果：研究结果显示EGFR与IGF-IR信号通路间存在潜在交互作用，这种相互作用影响细胞增殖、球体生长、扩散及迁移过程。同时记录了二维与三维细胞培养体系间的显著表型差异，以及MMPs表达水平的变化。 结论：两种乳腺癌细胞系在测试模型中均保持了公认的特征，同时展现出新的条件依赖性特性。总体而言，本研究深化了对EGFR与IGF-IR通路相互作用机制的理解，并凸显了三维模型在揭示不同乳腺癌表型背后关键生物学过程中的重要价值。
From Structure to Function: The Impact of EGFR and IGF-IR in 3D Breast Cancer Spheroids
肿瘤(癌症)患者之家