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vinculin 力传感器可检测肿瘤-破骨细胞相互作用。

Vinculin Force Sensor Detects Tumor-Osteocyte Interactions.

机构信息

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.

出版信息

Sci Rep. 2019 Apr 4;9(1):5615. doi: 10.1038/s41598-019-42132-x.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1032/6449341/298d986c1d1e/41598_2019_42132_Fig1_HTML.jpg

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