Cell Adhesiveness Serves as a Biophysical Marker for Metastatic Potential
Cell Adhesiveness Serves as a Biophysical Marker for Metastatic Potential
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DOI：
10.1158/0008-5472.can-19-1794
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发表时间：
2020-02-15
期刊：
影响因子：
11.2
通讯作者：
Engler, Adam J.
中科院分区：
文献类型：
--
作者：
Beri, Pranjali;Popravko, Anna;Engler, Adam J.
肿瘤是异质性的，由具有不同播散能力的细胞组成。尽管付出了巨大的努力，但没有通用的生物标志物作为实体瘤转移潜力的度量。然而，从这样的肿瘤中扩散的细胞的共同点是，当它们从肿瘤分离并通过基质迁移到血管内时，需要调节它们的粘附。即使在给定群体内的癌细胞中，粘附强度也是异质的，并且使用平行板流动室，我们将这些群体分离并分选为弱粘附组和强粘附组;当在基质条件下培养时，这种粘附表型在多天、分选循环中是稳定的，并且在所研究的所有上皮肿瘤系中是常见的。弱粘附细胞在二维和三维迁移试验中均显示迁移增加;这在培养中维持数天。亚群没有表现出差异的蛋白质参与的焦点粘附复合物的表达，但表现出内在的焦点粘附组装以及收缩的差异，导致差异表达的基因参与微管，细胞骨架连接，和电机活动。在人类乳腺肿瘤中，与弱粘附人群相关的基因表达导致更差的无进展和无疾病间隔。这些数据表明，粘附强度可以潜在地作为一个稳定的标记迁移和转移的潜力在一个给定的肿瘤人口和存在于肿瘤内的弱粘附细胞的分数可以作为一个物理marker for metastatic potential.Significance：癌细胞表现出异质性的粘附性，这可以用来预测转移的潜力。
Tumors are heterogeneous and composed of cells with different dissemination abilities. Despite significant effort, there is no universal biological marker that serves as a metric for metastatic potential of solid tumors. Common to disseminating cells from such tumors, however, is the need to modulate their adhesion as they detach from the tumor and migrate through stroma to intravasate. Adhesion strength is heterogeneous even among cancer cells within a given population, and using a parallel plate flow chamber, we separated and sorted these populations into weakly and strongly adherent groups; when cultured under stromal conditions, this adhesion phenotype was stable over multiple days, sorting cycles, and common across all epithelial tumor lines investigated. Weakly adherent cells displayed increased migration in both two-dimensional and three-dimensional migration assays; this was maintained for several days in culture. Subpopulations did not show differences in expression of proteins involved in the focal adhesion complex but did exhibit intrinsic focal adhesion assembly as well as contractile differences that resulted from differential expression of genes involved in microtubules, cytoskeleton linkages, and motor activity. In human breast tumors, expression of genes associated with the weakly adherent population resulted in worse progression-free and disease-free intervals. These data suggest that adhesion strength could potentially serve as a stable marker for migration and metastatic potential within a given tumor population and that the fraction of weakly adherent cells present within a tumor could act as a physical marker for metastatic potential.Significance: Cancer cells exhibit heterogeneity in adhesivity, which can be used to predict metastatic potential.