Temporal and molecular dynamics of human metastatic breast carcinoma cell adhesive interactions with human bone marrow endothelium analyzed by single-cell force spectroscopy.

Temporal and molecular dynamics of human metastatic breast carcinoma cell adhesive interactions with human bone marrow endothelium analyzed by single-cell force spectroscopy.
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DOI:
10.1371/journal.pone.0204418
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Glinsky VV
Glinsky VV
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xie L;Sun Z;Hong Z;Brown NJ;Glinskii OV;Rittenhouse-Olson K;Meininger GA;Glinsky VV

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骨是乳腺癌的常见转移部位,其转移机制尚未完全阐明。本研究的目的是利用原子力显微镜(AFM)以皮牛顿分辨率表征人乳腺癌细胞(HBCC)与人骨髓内皮(HBME)之间粘附相互作用的时间和分子动力学。在粘附实验中,将单个乳腺癌细胞MDA-MB-231 (MB231)或MDA-MB-435 (MB435)附着在AFM悬臂上,并在不同的时间段(0.5至300秒)与融合的HBME单层接触。破坏单个分子相互作用和完全分离相互作用细胞所需的力被分析为细胞-细胞粘附的措施。随着细胞-细胞接触时间从0.5秒延长到300秒,HBME与MB231或MB435细胞之间的粘附相互作用逐渐增加,这是由于单个粘附事件的数量和频率随时间的增加,以及随着时间的推移,更强的配体-受体相互作用的参与。对单个分子参与的研究表明,thomson - friedenreich抗原(TF-Ag)、半凝集素-3、整合素-β1和整合素-α3都以一种暂时确定的方式不同程度地促进HBCC/HBME粘附。总之,细胞-细胞接触时间增强HBCC对HBME的粘附,而这种粘附部分是由TF-Ag、半乳糖凝集素-3、整合素-α3和整合素-β1介导的。
Bone is a common site of metastasis for breast cancer and the mechanisms of metastasis are not fully elucidated. The purpose of our study was to characterize temporal and molecular dynamics of adhesive interactions between human breast cancer cells (HBCC) and human bone marrow endothelium (HBME) with piconewton resolution using atomic force microscopy (AFM). In adhesion experiments, a single breast cancer cell, MDA-MB-231 (MB231) or MDA-MB-435 (MB435) was attached to the AFM cantilever and brought into contact with a confluent HBME monolayer for different time periods (0.5 to 300 sec). The forces required to rupture individual molecular interactions and completely separate interacting cells were analyzed as measures of cell-cell adhesion. Adhesive interactions between HBME and either MB231 or MB435 cells increased progressively as cell-cell contact time was prolonged from 0.5 to 300 sec due to the time-dependent increase in the number and frequency of individual adhesive events, as well as to the involvement of stronger ligand-receptor interactions over time. Studies of the individual molecule involvement revealed that Thomsen-Friedenreich antigen (TF-Ag), galectin-3, integrin-β1, and integrin-α3 are all contributing to HBCC/HBME adhesion to various degrees in a temporally defined fashion. In conclusion, cell-cell contact time enhances adhesion of HBCC to HBME and the adhesion is mediated, in part, by TF-Ag, galectin-3, integrin-α3, and integrin-β1.
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