TY - JOUR
T1 - Cytokine-dependent invasiveness in B16 murine melanoma cells
T2 - Role of uPA system and MMP-9
AU - Bianchini, Francesca
AU - D'Alessio, Silvia
AU - Fibbi, Gabriella
AU - Del Rosso, Mario
AU - Calorini, Lido
PY - 2006/3
Y1 - 2006/3
N2 - Proteases are crucial for the spread of cancer cells from a primary tumor to the site of secondary growth. This study examined the ability of IFNγ and TNFα to stimulate a better invasiveness in B16 murine melanoma cells, and investigated whether this enhanced ability was related to a higher expression of protease activities, such as urokinase plasminogen activator (uPA) and its receptor (uPAR), and matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). We found that murine melanoma cells enhanced their lung-colonizing potential in vivo and invasiveness through Matrigel-coated filters upon costimulation with IFNγ and TNFα; neither IFNγ nor TNFα alone, at the dose used in the experiments, was able to elicit a change in the invasive/metastatic efficiency of melanoma cells. The invasive phenotype of murine melanoma cells stimulated with IFNγ and TNFα was characterized by an enhanced uPA/uPAR and MMP-9 expression: TNFα promoted MMP-9 mRNA expression and pro-MMP-9 protein secretion, and the costimulation with IFNγ and TNFα was required to potentiate the expression of mRNA and protein for uPAR, and to induce a redistribution of uPA from the soluble to the cell body-associated form. Both monoclonal antibodies, anti-uPAR and anti-MMP-9, caused a significant reduction of invasiveness in IFNγ/TNFα- stimulated melanoma cells. These results indicate that invasiveness in B16 murine melanoma cells can be regulated in a cytokine-specific fashion and is dependent on the synergism between the uPA/uPAR system and MMP-9.
AB - Proteases are crucial for the spread of cancer cells from a primary tumor to the site of secondary growth. This study examined the ability of IFNγ and TNFα to stimulate a better invasiveness in B16 murine melanoma cells, and investigated whether this enhanced ability was related to a higher expression of protease activities, such as urokinase plasminogen activator (uPA) and its receptor (uPAR), and matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). We found that murine melanoma cells enhanced their lung-colonizing potential in vivo and invasiveness through Matrigel-coated filters upon costimulation with IFNγ and TNFα; neither IFNγ nor TNFα alone, at the dose used in the experiments, was able to elicit a change in the invasive/metastatic efficiency of melanoma cells. The invasive phenotype of murine melanoma cells stimulated with IFNγ and TNFα was characterized by an enhanced uPA/uPAR and MMP-9 expression: TNFα promoted MMP-9 mRNA expression and pro-MMP-9 protein secretion, and the costimulation with IFNγ and TNFα was required to potentiate the expression of mRNA and protein for uPAR, and to induce a redistribution of uPA from the soluble to the cell body-associated form. Both monoclonal antibodies, anti-uPAR and anti-MMP-9, caused a significant reduction of invasiveness in IFNγ/TNFα- stimulated melanoma cells. These results indicate that invasiveness in B16 murine melanoma cells can be regulated in a cytokine-specific fashion and is dependent on the synergism between the uPA/uPAR system and MMP-9.
KW - Cell invasiveness
KW - IFNγ
KW - Lung metastasis
KW - Matrix metalloproteinases
KW - Murine melanoma cells
KW - TNFα
KW - uPA/uPAR system
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M3 - Article
C2 - 16465434
AN - SCOPUS:33645743458
VL - 15
SP - 709
EP - 714
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 3
ER -