Fuhrmann Alexander, Banisadr Afsheen, Beri Pranjali, Tlsty Thea D, Engler Adam J
Department of Bioengineering, University of California, San Diego, La Jolla, California.
Biomedical Sciences Program, University of California, San Diego, La Jolla, California.
Biophys J. 2017 Feb 28;112(4):736-745. doi: 10.1016/j.bpj.2016.12.038.
Cancer cells within a tumor are heterogeneous and only a small fraction are able to form secondary tumors. Universal biological markers that clearly identify potentially metastatic cells are limited, which complicates isolation and further study. However, using physical rather than biological characteristics, we have identified Mg- and Ca-mediated differences in adhesion strength between metastatic and nonmetastatic mammary epithelial cell lines, which occur over concentration ranges similar to those found in tumor stroma. Metastatic cells exhibit remarkable heterogeneity in their adhesion strength under stromal-like conditions, unlike their nonmetastatic counterparts, which exhibit Mg- and Ca-insensitive adhesion. This heterogeneity is the result of increased sensitivity to Mg- and Ca-mediated focal adhesion disassembly in metastatic cells, rather than changes in integrin expression or focal adhesion phosphorylation. Strongly adherent metastatic cells exhibit less migratory behavior, similar to nonmetastatic cell lines but contrary to the unselected metastatic cell population. Adhesion strength heterogeneity was observed across multiple cancer cell lines as well as isogenically, suggesting that adhesion strength may serve as a general marker of metastatic cells.
肿瘤内的癌细胞具有异质性，只有一小部分能够形成继发性肿瘤。能够明确识别潜在转移细胞的通用生物学标志物非常有限，这使得分离和进一步研究变得复杂。然而，利用物理而非生物学特性，我们已经确定了转移性和非转移性乳腺上皮细胞系之间镁和钙介导的黏附强度差异，这种差异发生的浓度范围与肿瘤基质中的浓度范围相似。与非转移性细胞系不同，转移性细胞在基质样条件下的黏附强度表现出显著的异质性，非转移性细胞系表现出对镁和钙不敏感的黏附。这种异质性是转移性细胞对镁和钙介导的黏着斑解体敏感性增加的结果，而不是整合素表达或黏着斑磷酸化的变化。与非转移性细胞系相似但与未分选的转移性细胞群体相反，强黏附的转移性细胞表现出较少的迁移行为。在多个癌细胞系中以及同基因细胞中均观察到黏附强度的异质性，这表明黏附强度可能作为转移性细胞的一个通用标志物。
