New DNBT article published in Cells


Replacement of the cantilever tip by a living cell in Atomic Force Microscopy (AFM) experiments permits the direct quantification of cell–substrate and cell–cell adhesion forces. This so-called single-cell probe force measurement technique has been employed in this work to differentiate between the adhesive capacities of parental and Sox2-overexpressing MCF7 breast cancer cells, having the latter a higher capacity for invasion and better resistance to endocrine therapy in vivo. Our findings demonstrate the strength of this combined approach to assess and compare the adhesion properties of different cell lines.

Single-Cell Probe Force Studies to Identify Sox2 Overexpression-Promoted Cell Adhesion in MCF7 Breast Cancer Cells

A scientific study by: J. Iturri, A. Weber, MdM. Vivanco and José L. Toca-Herrera

Cancer-induced alterations at the molecular level result in changes at the cellular and tissue level, leading to defects in cell proliferation, migration, and adhesion. Such adhesion dysregulation is crucial for cancer dissemination and the establishment of metastasis in other tissues with vastly different microenvironments.

Adhesion in cell–cell and cell–extracellular matrix (ECM) interactions is mediated by transmembrane protein receptors, such as cadherins, integrins, and proteoglycans. The intracellular side of these receptors interacts with cytoplasmic proteins, including the cytoskeleton, while the extracellular side binds to specific partners in the ECM. Such interplay between cells and ECM components triggers the transduction of the sensed signal via signaling pathways, which influence cell motility, proliferation, and the final mechanical properties of cells. Altered expression profiles of ECM components have been found to correlate with tumorigenesis, tissue invasiveness, metastatic behavior, and survival in many types of cancer, including breast cancer. Then, development of an in vitro approach for the detection of such alterations might turn very useful.

Here we show the use of single-cell probe AFM force–distance measurements, based on a self-designed protocol, to determine the adhesion strength of both parental and Sox2 overexpressing MCF7 cells, quantifying cell-fibronectin (a large ECM glycoprotein that carries binding sites for both integrins as well as syndecans), as well as cell–cell interactions (homo- vs heterotypic). Through variation in cell–surface and cell–cell contact time, ranging from 0 to 120 s, we have been able to study the attractive interaction in a time-dependent manner.

 

This article has been published in Cells 2020, 9(4), 935: https://doi.org/10.3390/cells9040935


13.05.2020