Zhu Peiran, Tseng Ning-Hsuan, Xie Tianfa, Li Ningwei, Fitts-Sprague Isaac, Peyton Shelly R, Sun Yubing
ACS Biomater Sci Eng. 2019 Aug 12;5(8):3817-3827. doi: 10.1021/acsbiomaterials.8b00861. Epub 2019 Jan 28.
Fusion of cancer cells is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have demonstrated that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive area of the patterned substrates, reducing cytoskeletal tensions pharmacologically, altering matrix stiffness, and modulating pattern curvature all supported the spontaneous fusion and stability of these multinucleated giant cells. These observations highlight that the biomechanical microenvironment of cancer cells, including the matrix rigidity and interfacial curvature, can directly modulate their fusogenicity, an unexplored mechanism through which biophysical cues regulate tumor progression.
癌细胞融合被认为有助于肿瘤发展和耐药性。细胞融合事件的低频率以及融合细胞的不稳定性阻碍了我们对控制细胞融合分子机制的理解。我们已经证明，几种乳腺癌细胞系在体外可融合形成多核巨细胞，并且融合细胞的起始和寿命可仅由生物物理因素调节。动态调节图案化底物的粘附面积、通过药理学方法降低细胞骨架张力、改变基质硬度以及调节图案曲率，均支持这些多核巨细胞的自发融合和稳定性。这些观察结果突出表明，癌细胞的生物力学微环境，包括基质刚度和界面曲率，可直接调节其融合能力，这是生物物理线索调节肿瘤进展的一种未被探索的机制。
