[en] Tumor progression requires the dispersion of epithelial cells from neoplastic clusters and cell invasion of adjacent stromal connective tissue. Aiming at demonstrating the precise relationships between cell dispersion and cell invasion, related respectively to expression of E-cadherin/catenin complex and matrix metalloproteinases (MMPs), we developed an original in vitro model of cell dispersion analysis. Our study reports the validation of this model that allowed us to analyze and quantify the cell cohesion level by means of time-lapse videomicroscopy and computer analysis based on the observation of spatial and temporal cell distribution. Our model was able to distinguish 2 groups among different human bronchial and mammary epithelial cells previously characterized for the expression of E-cadherin/catenin complex and MMPs and their invasive capacity in the Boyden chamber assay. The first group (16HBE14o-, MCF-7, T47D) that expressed membranous E-cadherin and -catenin, and was negative for MMP-2 expression and non-invasive, displayed a highly cohesive pattern corresponding to a cluster spatial distribution. The second group (Beas2B, BZR, BZR-T33, MDA-MB-231, MDA-MB-435, BT549 and HS578T) that was invasive and showed lack of expression of E-cadherin and a cytoplasmic redistribution of -catenin, displayed a dispersed pattern corresponding to a random spatial distribution. Downregulation of E-cadherin by a blocking antibody induced a more random distribution. Conversely, expression of E-cadherin by cDNA transfection induced a cluster distribution. Moreover, tumor cell lines that co-expressed MT1-MMP and MMP-2 (Beas2B, BZR, BZR-T33, MDA-MB-435, BT549 and HS578T) showed a more dispersed pattern than tumor cell lines that did not express MMP-2 (MDA-MB-231). In conclusion, we demonstrated that the spatial group behavior of cell lines, i.e., their cohesion/dispersion ability, reflects their invasive properties. Thus, this model of cell dispersion analysis may represent a new test to measure tumor cell aggressiveness.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nawrocki-Raby, Béatrice; CHU Maison Blanche (Reims, France) > INSERM U514
Polette, Myriam; CHU Maison Blanche (Reims, France) > INSERM U514
Gilles, Christine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Clavel, Christine; CHU Maison Blanche (Reims, France) > INSERM U514
Strumane, Kristin; VIB-Ghent University > Department of Molecular Biology
Matos, Manuela; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Zahm, Jean-Marie; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Van Roy, Franz; VIB-Ghent University > Department of Molecular Biology
Bonnet, Noël; CHU Maison Blanche (Reims, France) > INSERM U514
Birembaut, Philippe; CHU Maison Blanche (Reims, France) > INSERM U514
Language :
English
Title :
Quantitative cell dispersion analysis: new test to measure tumor cell aggressiveness
Publication date :
2001
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
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