Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN, 46202, USA.
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, 46202, USA.
Sci Rep. 2019 Apr 4;9(1):5615. doi: 10.1038/s41598-019-42132-x.
This study utilized a Förster resonance energy transfer (FRET)-based molecular tension sensor and live cell imaging to evaluate the effect of osteocytes, a mechanosensitive bone cell, on the migratory behavior of tumor cells. Two cell lines derived from MDA-MB-231 breast cancer cells were transfected with the vinculin tension sensor to quantitatively evaluate the force in focal adhesions of the tumor cell. Tumor cells treated with MLO-A5 osteocyte-conditioned media (CM) decreased the tensile forces in their focal adhesions and decreased their migratory potential. Tumor cells treated with media derived from MLO-A5 cells exposed to fluid flow-driven shear stress (FFCM) increased the tensile forces and increased migratory potential. Focal adhesion tension in tumor cells was also affected by distance from MLO-A5 cells when the two cells were co-cultured, where tumor cells close to MLO-A5 cells exhibited lower tension and decreased cell motility. Overall, this study demonstrates that focal adhesion tension is involved in altered migratory potential of tumor cells, and tumor-osteocyte interactions decrease the tension and motility of tumor cells.
本研究利用基于Förster 共振能量转移（FRET）的分子张力传感器和活细胞成像技术，评估破骨细胞（一种机械敏感的骨细胞）对肿瘤细胞迁移行为的影响。两种源自 MDA-MB-231 乳腺癌细胞的细胞系转染了整联蛋白张力传感器，以定量评估肿瘤细胞黏附斑中的力。用 MLO-A5 破骨细胞条件培养基（CM）处理的肿瘤细胞减少了黏附斑中的张力并降低了迁移能力。用暴露于流体流动驱动剪切力（FFCM）的 MLO-A5 细胞的培养基处理的肿瘤细胞增加了张力并增加了迁移能力。当两种细胞共培养时，肿瘤细胞与 MLO-A5 细胞的距离也会影响肿瘤细胞的黏附斑张力，靠近 MLO-A5 细胞的肿瘤细胞表现出较低的张力和降低的细胞迁移能力。总的来说，本研究表明黏附斑张力参与了肿瘤细胞迁移能力的改变，肿瘤-破骨细胞相互作用降低了肿瘤细胞的张力和迁移能力。
