Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP.
The newly established breast cancer cell line G3S1, derived from EM-G3 breast cancer progenitors, was analyzed for functional changes related to neoplastic progression manifested by elevated invasiveness and enhanced capability to degrade gelatin. Degradation of gelatin and invasiveness of G3S1 cells was found to be dependent on the activity of matrix proteinases and actin cytoskeletal dynamics. Therefore, the expression and activity of these proteases was compared in G3S1 and EM-G3 cells. Despite enhanced capability of G3S1 cells to degrade gelatin, these cells exhibited lower levels of secreted extracellular matrix degrading proteases than parental EM-G3 cells. However, the expression of membrane-bound MT1-MMP was strongly elevated in G3S1 cells. While the degradation of gelatin was associated with invadopodia-like structures in both EM-G3 and G3S1 cells, the cytoskeletal remodeling dynamics was greatly elevated in G3S1 cells, suggesting that upregulation of MT1-MMP, together with elevation of cytoskeletal remodeling dynamics can effectively cause elevated invasiveness and enhanced matrix degrading capability in G3S1 cells.
Tolde
Ondrej
O
Department of Cell Biology, Faculty of Science, Charles University in Prague, 128 43 Prague, Czech Republic.
Rösel
Daniel
D
Mierke
Claudia T
CT
Panková
Daniela
D
Folk
Petr
P
Vesely
Pavel
P
Brábek
Jan
J
D000199:Actins / Q000378:metabolism*; D007611:Aprotinin / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D011554:Pseudopodia / Q000201:enzymology; D015854:Up-Regulation
D000199:Actins; D004151:Dipeptides; D008387:Marine Toxins; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D005780:Gelatin; D007611:Aprotinin; D053505:Matrix Metalloproteinases, Secreted; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D007930:Leucine; C024974:E 64