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Role of cellular adhesions in tissue dynamics spectroscopy

机译:细胞粘附在组织动力学光谱中的作用

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Cellular adhesions play a critical role in cell behavior, and modified expression of cellular adhesion compounds has been linked to various cancers. We tested the role of cellular adhesions in drug response by studying three cellular culture models: three-dimensional tumor spheroids with well-developed cellular adhesions and extracellular matrix (ECM), dense three-dimensional cell pellets with moderate numbers of adhesions, and dilute three-dimensional cell suspensions in agarose having few adhesions. Our technique for measuring the drug response for the spheroids and cell pellets was biodynamic imaging (BDI), and for the suspensions was quasi-elastic light scattering (QELS). We tested several cytoskeletal chemotherapeutic drugs (nocodazole, cytochalasin-D, paclitaxel, and colchicine) on three cancer cell lines chosen from human colorectal adenocarcinoma (HT-29), human pancreatic carcinoma (MIA PaCa-2), and rat osteosarcoma (UMR-106) to exhibit differences in adhesion strength. Comparing tumor spheroid behavior to that of cell suspensions showed shifts in the spectral motion of the cancer tissues that match predictions based on different degrees of cell-cell contacts. The HT-29 cell line, which has the strongest adhesions in the spheroid model, exhibits anomalous behavior in some cases. These results highlight the importance of using three-dimensional tissue models in drug screening with cellular adhesions being a contributory factor in phenotypic differences between the drug responses of tissue and cells.
机译:细胞粘附在细胞行为中起关键作用,并且细胞粘附化合物的修饰表达已与多种癌症相关。通过研究三种细胞培养模型,我们测试了细胞粘附在药物反应中的作用:具有发达的细胞粘附和细胞外基质(ECM)的三维肿瘤球体,具有中等粘附数目的致密三维细胞沉淀和稀释了三种琼脂糖中的三维细胞悬浮液几乎没有粘附。我们用于测量球体和细胞沉淀的药物反应的技术是生物动力学成像(BDI),而用于悬浮液的是准弹性光散射(QELS)。我们在选自人结肠直肠腺癌(HT-29),人胰腺癌(MIA PaCa-2)和大鼠骨肉瘤(UMR-)的三种癌细胞系上测试了几种细胞骨架化学治疗药物(诺考达唑,细胞松弛素D,紫杉醇和秋水仙碱) 106)表现出不同的粘合强度。将肿瘤球体的行为与细胞悬浮液的行为进行比较表明,癌症组织的光谱运动发生了变化,这与基于不同程度的细胞-细胞接触的预测相符。在球体模型中具有最强粘附力的HT-29细胞系在某些情况下表现出异常行为。这些结果突出了在药物筛选中使用三维组织模型的重要性,其中细胞粘附是组织和细胞药物反应之间的表型差异的一个促成因素。

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