Kittur Harsha, Tay Andy, Hua Avery, Yu Min, Di Carlo Dino
University of California Los Angeles, Los Angeles, California.
University of Southern California, Los Angeles, California.
Biophys J. 2017 Oct 17;113(8):1858-1867. doi: 10.1016/j.bpj.2017.08.028.
In this work, we introduce, to our knowledge, a new set of adhesion-based biomarkers for characterizing mammalian cells. Mammalian cell adhesion to the extracellular matrix influences numerous physiological processes. Current in vitro methods to probe adhesion focus on adhesive force to a single surface, which can investigate only a subcomponent of the adhesive, motility, and polarization cues responsible for adhesion in the 3D tissue environment. Here, we demonstrate a method to quantify the transhesive properties of cells that relies on the microscale juxtaposition of two extracellular matrix-coated surfaces. By multiplexing this approach, we investigate the unique transhesive profiles for breast cancer cells that are adapted to colonize different metastatic sites. We find that malignant breast cancer cells readily transfer to new collagen I surfaces, and away from basement membrane proteins. Integrins and actin polymerization largely regulate this transfer. This tool can be readily adopted in cell biology and cancer research to uncover, to our knowledge, novel drivers of adhesion (or de-adhesion) and sort cell populations based on complex phenotypes with physiological relevance.
在本研究中,据我们所知,我们引入了一组用于表征哺乳动物细胞的基于黏附的新型生物标志物。哺乳动物细胞与细胞外基质的黏附影响众多生理过程。当前用于探测黏附的体外方法聚焦于对单一表面的黏附力,这只能研究在三维组织环境中负责黏附的黏附、运动和极化线索的一个子成分。在此,我们展示了一种量化细胞跨黏附特性的方法,该方法依赖于两个细胞外基质包被表面的微观并列。通过复用这种方法,我们研究了适应于在不同转移位点定植的乳腺癌细胞独特的跨黏附谱。我们发现恶性乳腺癌细胞很容易转移到新的I型胶原表面,并远离基底膜蛋白。整合素和肌动蛋白聚合在很大程度上调节这种转移。据我们所知,该工具可轻易应用于细胞生物学和癌症研究,以揭示新的黏附(或去黏附)驱动因素,并基于具有生理相关性的复杂表型对细胞群体进行分类。