title: Cell-Cell Adhesion and Cytoskeleton Tension Oppose Each Other in Regulating Tumor Cell Aggregation.
abstract: Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion; however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the resulting cell motility on the substrate. We report here a highly reproducible, automated, microscopy-based quantification of tumor-cell spheroid formation in the absence of cell-substrate adhesion and use it to characterize cell aggregation dynamics in the early steps of this process. This method is based on fluorescence and bright-field microscopy and on a custom MATLAB program to quantify automatically the cells' aggregation kinetics. We demonstrate that the cell-cell adhesion protein E-cadherin and the desmosome proteins DSG2 and DSC2 are important for aggregation. Furthermore, we show that inhibition or silencing of myosin IIa enhances aggregation, suggesting that cytoskeleton tension inhibits tumor cell aggregation. This work opens new avenues to study the principles that govern multicellular aggregation, to characterize the aggregation properties of various tumor cell types, as well as to screen for drugs that inhibit or promote aggregation.
authors: Université de Toulouse, ITAV-USR3505, Toulouse, France. CNRS, ITAV-USR3505, Toulouse, France.
authors: Laure
authors: L
authors: Saias
authors: Université de Toulouse, ITAV-USR3505, Toulouse, France. CNRS, ITAV-USR3505, Toulouse, France.
authors: Aurélie
authors: A
authors: Gomes
authors: Université de Toulouse, ITAV-USR3505, Toulouse, France. CNRS, ITAV-USR3505, Toulouse, France.
authors: Martine
authors: M
authors: Cazales
authors: Université de Toulouse, ITAV-USR3505, Toulouse, France. CNRS, ITAV-USR3505, Toulouse, France. CHU de Toulouse, Toulouse, France. valerie.lobjois@itav.fr bernard.ducommun@itav.fr.
authors: Bernard
authors: B
authors: Ducommun
authors: Université de Toulouse, ITAV-USR3505, Toulouse, France. CNRS, ITAV-USR3505, Toulouse, France. valerie.lobjois@itav.fr bernard.ducommun@itav.fr.
authors: Valérie
authors: V
authors: Lobjois
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000473:pathology; D051187:Desmocollins / Q000378:metabolism; D051301:Desmoglein 2 / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
chemical_list: D015820:Cadherins; C081561:DSC2 protein, human; C495314:DSG2 protein, human; D051187:Desmocollins; D051301:Desmoglein 2