Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, United States.
Biomacromolecules. 2024 Apr 8;25(4):2338-2347. doi: 10.1021/acs.biomac.3c01217. Epub 2024 Mar 18.
Bone is a frequent site for metastatic development in various cancer types, including breast cancer, with a grim prognosis due to the distinct bone environment. Despite considerable advances, our understanding of the underlying processes leading to bone metastasis progression remains elusive. Here, we applied a bioactive three-dimensional (3D) model capable of mimicking the endosteal bone microenvironment. MDA-MB-231 and MCF7 breast cancer cells were cultured on the scaffolds, and their behaviors and the effects of the biomaterial on the cells were examined over time. We demonstrated that close interactions between the cells and the biomaterial affect their proliferation rates and the expression of c-Myc, cyclin D, and KI67, leading to cell cycle arrest. Moreover, invasion assays revealed increased invasiveness within this microenvironment. Our findings suggest a dual role for endosteal mimicking signals, influencing cell fate and potentially acting as a double-edged sword, shuttling between cell cycle arrest and more active, aggressive states.
骨骼是包括乳腺癌在内的多种癌症类型转移发展的常见部位，由于独特的骨骼环境，预后较差。尽管取得了相当大的进展，但我们对导致骨转移进展的潜在过程的理解仍然难以捉摸。在这里，我们应用了一种能够模拟骨内膜骨微环境的生物活性三维（3D）模型。将 MDA-MB-231 和 MCF7 乳腺癌细胞培养在支架上，随着时间的推移，检查细胞的行为和生物材料对细胞的影响。我们证明，细胞与生物材料之间的紧密相互作用会影响它们的增殖率和 c-Myc、细胞周期蛋白 D 和 KI67 的表达，导致细胞周期停滞。此外，侵袭实验显示，在这种微环境中，侵袭性增加。我们的研究结果表明，骨内膜模拟信号具有双重作用，影响细胞命运，并可能充当双刃剑，在细胞周期停滞和更活跃、更具侵袭性的状态之间转换。
