[Cell phenotype determines PAI-1 antiproliferative effect - suppressed proliferation of the lung cancer but not prostate cancer cells].
BACKGROUND
Plasminogen inhibitor activator type 1 (PAI-1) is an important regulator of tumor growth and metastasis formation acting directly via specific urokinase complexing or indirectly due to its affinity to vitronectin. We have shown previously that PAI-1 modifies angiogenic activity of endothelial cells in a dose-dependent manner but also in close relationship to the cell phenotype. Present study aimed on evaluating the PAI-1 effect on the proliferative activity of lung cancer cells (A549), prostate cancer cells (DU145) as well as endothelial cells (HUVEC).


RESULTS
Mutated PAI-1 (1, 10, 100 microg/mL) characterized by the prolonged antifibrinolytic activity (T1/2 approximately 7000 h) inhibited proliferation of lung cancer A549 cells in a dose-dependent (p < 0.001) and time-dependent (p < 0.001) manner. No significant effect on the DU145 prostate cancer cells has been observed except of the 72 h cultures with highest PAI-1 concentration (100 microg/ml) (p < 0.001). Proliferative activity of endothelial cells (HUVEC) was affected by 100 microg/ml PAI-1 only, and independent of the culture period (24, 48 and 72 h, p < 0.001).


CONCLUSIONS
Plasminogen inhibitor activator type 1 modulates cell proliferation via antifibrynolitic mechanizm time- and dose-dependently, however final outcome is strongly affected by the cell phenotype.
Chorostowska-Wynimko
Joanna
J
Samodzielna Pracownia Diagnostyki Molekularnej i Immunologii, Instytut Gruźlicy i Chorób Płuc w Warszawie, ul. Płocka 26, 01-138 Warszawa. immuno@igichp.edu.pl
Kedzior
Marta
M
Struniawski
Radosław
R
Jaguś
Paulina
P
Skrzypczak-Jankun
Ewa
E
Jankun
Jerzy
J
D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000145:classification / Q000187:drug effects / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D014568:Urokinase-Type Plasminogen Activator