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G-CSF increases secretion of urokinase-typeplasminogen activator by human lung cancer cells

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We reported previously that granulocyte colony-stimulating factor (G-CSF) can promote the invasion ofhuman lung cancer cell lines in vitro. However, the exact mechanism of its stimulatory effect on invasionremains to be elucidated. In the present study we mainly focused our attention on the components of theplasminogen activation system in human lung cancer cell lines, because of the central role that plasminogenactivators play in regulating extracellular proteolysis. We showed that G-CSF induced a dose-dependentincrease in the urokinase-type plasminogen activator (uPA) activity in the conditioned medium of a PC-9lung cancer cell line. When the amounts of uPA activity were quantitated by densitometry, we found thateven at a concentration of 0.01 mg/ml, G-CSF had a stimulatory effect on the uPA release, while highconcentrations caused a 3.6-fold increase at a maximum concentration of 1 mg/ml. A Western blot analysisof the conditioned medium confirmed the findings observed in a zymographic analysis. The observed increasein uPA protein was paralleled by a significant increase in the uPA mRNA levels after treatment withG-CSF. However, our experiments failed to identify any alteration in the plasminogen activator inhibitor(PAI) secretion caused by G-CSF. In addition, we also found the expression of G-CSF receptor by PC-9cells, suggesting the possible pathway activated by G-CSF.©Kluwer Academic Publishers

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Pei, XH., Nakanishi, Y., Takayama, K. et al. G-CSF increases secretion of urokinase-typeplasminogen activator by human lung cancer cells. Clin Exp Metastasis 16, 551–558 (1998). https://doi.org/10.1023/A:1006546402703

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