TY - JOUR
T1 - Modulation of urokinase-type plasminogen activator and metalloproteinase activities in cultured mouse mammary-carcinoma cells
T2 - Enhancement by paclitaxel and inhibition by nocodazole
AU - Alonso, Daniel F.
AU - Farina, Hernán G.
AU - Arregui, Carlos
AU - Aon, Miguel A.
AU - Gomez, Daniel E.
PY - 1999
Y1 - 1999
N2 - Paclitaxel is a potent anti-tumor drug used in the treatment of breast cancer. It induces de-centralization of the microtubular system in tumor cells, blocking cell division. In the search for dissemination to a secondary site, cancer cells are capable of degrading most components of the extracellular matrix via an extracellular proteolytic cascade, including urokinase-type plasminogen activator (uPA) and the matrix metalloproteinases (MMPs). In the present study, the effects of paclitaxel and nocodazole, 2 drugs known to affect microtubules with opposite mechanisms of action, have been tested for their effect on the secretion of uPA and MMPs in cultures of F311 mouse mammary-tumor cells. Tumor-derived uPA activity significantly increased after pre-treatment of tumor cells for 24 hr with micromolar concentrations of paclitaxel (4 μM), while decreasing after pre-treatment with nocodazole (1 μM). A similar modulation was found for MMP-9 by zymographic analysis. Immunofluorescence and Westernblot analysis confirmed the formation of parallel microtubule fragments in paclitaxel-treated cells and almost complete de-polymerization of microtubules in nocodazole-treated ones. Our data suggest that, through opposite actions on microtubule organization and dynamics, paclitaxel and nocodazole exert inverse modulation of tumor-derived proteolytic activity in mammary tumor cells.
AB - Paclitaxel is a potent anti-tumor drug used in the treatment of breast cancer. It induces de-centralization of the microtubular system in tumor cells, blocking cell division. In the search for dissemination to a secondary site, cancer cells are capable of degrading most components of the extracellular matrix via an extracellular proteolytic cascade, including urokinase-type plasminogen activator (uPA) and the matrix metalloproteinases (MMPs). In the present study, the effects of paclitaxel and nocodazole, 2 drugs known to affect microtubules with opposite mechanisms of action, have been tested for their effect on the secretion of uPA and MMPs in cultures of F311 mouse mammary-tumor cells. Tumor-derived uPA activity significantly increased after pre-treatment of tumor cells for 24 hr with micromolar concentrations of paclitaxel (4 μM), while decreasing after pre-treatment with nocodazole (1 μM). A similar modulation was found for MMP-9 by zymographic analysis. Immunofluorescence and Westernblot analysis confirmed the formation of parallel microtubule fragments in paclitaxel-treated cells and almost complete de-polymerization of microtubules in nocodazole-treated ones. Our data suggest that, through opposite actions on microtubule organization and dynamics, paclitaxel and nocodazole exert inverse modulation of tumor-derived proteolytic activity in mammary tumor cells.
UR - http://www.scopus.com/inward/record.url?scp=0032870178&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032870178&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19991008)83:2<242::AID-IJC16>3.0.CO;2-8
DO - 10.1002/(SICI)1097-0215(19991008)83:2<242::AID-IJC16>3.0.CO;2-8
M3 - Article
C2 - 10471534
AN - SCOPUS:0032870178
SN - 0020-7136
VL - 83
SP - 242
EP - 246
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -