Reactive oxygen species regulate the generation of urokinase plasminogen activator in human hepatoma cells via MAPK pathways after treatment with hepatocyte growth factor

Tumor cells are known to produce larger amounts of reactive oxygen species (ROS) than normal cells. Although numerous reports have indicated the importance of ROS in urokinase plasminogen activator (uPA) production, the precise mechanisms remain controversial. In our study, we investigated the effect of ROS on uPA generation in human hepatoma cells, HepG2 and Hep 3B. We determined the effects of hepatocyte growth factor (HGF) on the regulation of ROS, which resulted in suppression of ROS production, as measured with the fluorescent probe, 2'-7'-dichlorofluorescein diacetate. The role of HGF in modulating ROS production, particularly that regulated by Rac-1, was determined. HGF suppressed the increment in Rac-1-regulated ROS in both cell lines. Treatment with 200 microM of H2O2 showed a 1.6-2.1 fold increment in HGF, but a little increment occurred at 500 microM of H2O2. It looks no dose dependent manner. Combined treatment with H2O2 and HGF, resulted in a slightly increased production of HGF compared to no treatment (control). Also, H2O2 upregulated uPA expression in both hepatoma cell lines. To identify the downstream pathways regulated by ROS, we treated cells with PD 98059, an MEK inhibitor, and SB 203580, a p38 inhibitor, after treatment with H2O2, and showed negative control between ERK and p38 kinase activities for uPA regulation. We found that HGF modulate Rac-1-regulated ROS production through activation of Akt and ROS regulates uPA production via MAP kinase, which provides a novel clue to clarify the mechanism underlying hepatoma progression.

Expression of urokinase: type plasminogen activator, its receptor, and its inhibitor in gastric adenocarcinoma tissues

The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis. This study was conducted to investigate the role of uPA, uPAR and PAI-1 in the invasion and metastasis of gastric adenocarcinoma. The expression of mRNAs for uPA and PAI-1 was determined by Northern blot analysis in nine primary gastric cancer tissues, nine paired metastatic lymph nodes and normal gastric mucosa. The mRNA of uPA was not or faintly detected in normal mucosa, while the expression was increased in both primary gastric cancer tissues and metastatic lymph nodes to a similar degree. The mRNA expression for PAI-1 in the gastric cancer tissues was not different from that in the paired metastatic lymph nodes and normal mucosae. uPAR was determined by immunohistochemical staining, demonstrating that five (56%) and six (67%) out of nine primary gastric cancer tissues and nine paired metastatic lymph nodes were positive, respectively and the intensity was stronger in metastatic lymph nodes. The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR, and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis.

Relación entre el activador del plasminógeno tipo urocinasa y el cáncer: mecanismo de regulación y control / Relation between urokinase-type plasminogen activator and cancer mechanims of regulation and control

Son analizados y discutidos los aspectos fisiológicos, bioquímicos y reguladores de la formación de plasmina por el activador de plasminógeno tipo urocinasa (uAP), así como su relación con el cáncer. En el cáncer, la activación del plasminógeno en la superficie celular ha mostrado ser esencial en la degradación de la matriz extracelular, en la disolución de la membrana basal, en los procesos de invasión y en las metástasis. La capacidad de las células para producir plasmina sobre su superficie celular depende de la presencia de uAP y del receptor del plasminógeno; ambos son las base de la regulación del sistema activante del plasminógeno in vivo

Enhanced expression of urokinase-type plasminogen activator in the rat endometrium following induction of decidualisation.

Urokinase-type plasminogen activator(uPA) assayed in uteri of cycling and deciduoma bearing rats shows detectable levels of this enzyme in endometrium. Zymographic analysis confirms uPA of decidual tissue and, following artificial induction of decidualisation, uPA activity constantly increases in the decidualising endometrium reaching a peak on day 9 of pseudopregnancy. Endometrial uPA of nonpregnant rats does not show any significant change during estrous cycle. Results are discussed in relation to expression of this activator in endometrium of rats during morphogenesis of decidual cells.

Lys-plasminógeno / Lys-plasminogen

Los fibrinolíticos (Estreptoquinasa y Uroquinasa) transforman el plasminógeno circulante en plasmina pero actúan poco sobre la fibrina de los trombos. El lys-plasminógeno de origen placentario se fija a la fibrina de los trombos, de modo que al ser activado por los fibrinolíticos promueve la trombólisis y la disolución de los coágulos. con ello se abren nuevas perspectivas a la terapia fibrinolítica en la enfermedad tromboembólica; las obstrucciones arteriales agudas de las extremidades inferiores y en las trombosis coronarias y cerebrales