Hyaluronic acid (HA) has been implicated in cell adhesion, motility, and tumor progression in gliomas. We previously reported that HA stimulates secretion of matrix metalloproteinase-9 (MMP-9) and induces glioma invasion. However, the molecular mechanism of HA action and therapeutic strategies for blocking HA-induced MMP-9 secretion remain unknown. Here, we report that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) blocks MMP-9 secretion and that HA-induced nuclear factor-KB (NF-KB) activation is mediated by IKB kinase, which phosphorylates the NF-KB inhibitor IKBA and promotes its degradation. In addition, using an RNA interference approach, we show that the focal adhesion kinase plays a critical role in mediating HA-induced NF-KB activation, which resulted in increased MMP-9 expression and secretion, cell migration, and invasion. Importantly, we show that 17-AAG acts by blocking focal adhesion kinase activation, thereby inhibiting IKB kinasedependent IKBA phosphorylation/degradation, NF-KB activation, and MMP-9 expression. This leads to suppression of HA-induced cell migration and invasion. Based on our data, we propose that 17-AAG is a candidate drug for treatment of highly invasive gliomas resulting from HA-induced, NF-KB -mediated MMP-9
Characteristics of benthic microalgae and sediment properties were investigated for the intertidal flats of Kwangyang Bay, Korea. Sampling stations were selected every 100 m in the intertidal flats from land-side to open ocean at two different sampling sites. Samples were collected in June 2004, July, September, November, February and May 2005. Sediments properties were measured including temperature, water contents, sediment bulk density, nutrient concentrations in porewater. Chlorophyll a concentrations in surface sediment (0.5 cm) were measured and relationships between the chlorophyll a and various sediment properties were analyzed to identify major mechanisms regulating biomass of benthic microalgae in the intertidal flats using simple linear regression analysis. Sediment chlorophyll a concentrations were maximum during winter and minimum during warm seasons ranging from 4.4 mg m -2 to 81.2 mg m -2. No clear spatial variations were observed for the sediment chlorophyll a in the study sites. Results from regression analysis suggested that benthic microalgae biomass was affected by sediment temperature and nutrients especially ammonium and silicate. Grazing effect was estimated using chlorophyll: pheopigments ratio, indirect indicator of grazing activity, and the positive correlation of the ratio and chlorophyll a implied that microalgae biomass is affected by grazing of zoobenthos although direct measurement of grazing activity is required to determine the importance of top-down controls in the benthic microalgae dynamics.
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