Expression pattern of the urokinase-plasminogen activator system in rat DS-sarcoma: Role of oxygenation status and tumour size

The urokinase plasminogen activator system plays a central role in malignant tumour progression. Both tumour hypoxia and enhancement of urokinase plasminogen activator, urokinase plasminogen activator-receptor and plasminogen activator inhibitor type 1 have been identified as adverse prognostic factors. Upregulation of urokinase plasminogen activator or plasminogen activator inhibitor type 1 could present means by which hypoxia influences malignant progression. Therefore, the impact of hypoxia on the expression pattern of the urokinase plasminogen activator system in rat DS-sarcoma in vivo and in vitro was examined. In the in vivo setting, tumour cells were implanted subcutaneously into rats, which were housed under either hypoxia, atmospheric air or hyperoxia. For in vitro studies, DS-sarcoma cells were incubated for 24 h under hypoxia. Urokinase plasminogen activator and urokinase plasminogen activator-receptor expression were analysed by flow cytometry. Urokinase plasminogen activator activity was measured using zymography. Plasminogen activator inhibitor type 1 protein levels in vitro and in vivo were examined with ELISA. PAI-1 mRNA levels were determined by RT–PCR. DS-sarcoma cells express urokinase plasminogen activator, urokinase plasminogen activator-receptor, and plasminogen activator inhibitor type 1 in vitro and in vivo. The urokinase plasminogen activator activity is enhanced in DS-sarcomas compared to normal tissues and rises with increasing tumour volume. The oxygenation level has no impact on the urokinase plasminogen activator activity in cultured DS-sarcoma cells or in solid tumours, although in vitro an increase in plasminogen activator inhibitor type 1 protein and mRNA expression after hypoxic challenge is detectable. The latter plasminogen activator inhibitor type 1 changes were not detectable in vivo. Hypoxia has been demonstrated to contribute to the upregulation of some components of the system in vitro, although this effect was not reproducible in vivo. This may indicate that the serum level of plasminogen activator inhibitor type 1 is not a reliable surrogate marker of tumour hypoxia

Deep slab hydration induced by bending-related variations in tectonic pressure

Bending of oceanic plates at subduction zones results in extension and widespread normal faulting(1) in the upper, brittle part of the slab(2,3). Detailed seismic surveys at trenches reveal that this part of the oceanic plate could be pervasively hydrated for several kilometres below the crust-mantle boundary(4-7). Similarly, heat-flow surveys indicate active fluid circulation within the slab(8). Yet, the mechanisms that enable fluids to percolate to such depths in spite of their natural buoyancy remain unclear. Here we use two-dimensional numerical experiments to show that stress changes induced by the bending oceanic plate produce subhydrostatic or even negative pressure gradients along normal faults, favouring downward pumping of fluids. The fluids then react with the crust and mantle surrounding the faults and are stored in the form of hydrous minerals. We suggest that this process is the dominant mechanism of deep slab hydration, although it may be locally aided by the enhancement in porosity due to prefailure dilatancy(9), pre-existing cracks(10) and migrating fluid-filled cracks(11). Our results have implications for the transport of water into the deeper parts of the mantle(12), and for further clarifying the seismic anisotropy of slabs(13)

Fault-induced seismic anisotropy by hydration in subducting oceanic plates

International audienceThe variation of elastic- wave velocities as a function of the direction of propagation through the Earth's interior is a widely documented phenomenon called seismic anisotropy. The geometry and amount of seismic anisotropy is generally estimated by measuring shearwave splitting, which consists of determining the polarization direction of the fast shear- wave component and the time delay between the fast and slow, orthogonally polarized, waves. In subduction zones, the teleseismic fast shear- wave component is oriented generally parallel to the strike of the trench(1), although a few exceptions have been reported (Cascadia(2) and restricted areas of South America(3,4)). The interpretation of shear- wave splitting above subduction zones has been controversial and none of the inferred models seems to be sufficiently complete to explain the entire range of anisotropic patterns registered worldwide(1). Here we show that the amount and the geometry of seismic anisotropies measured in the forearc regions of subduction zones strongly depend on the preferred orientation of hydrated faults in the subducting oceanic plate. The anisotropy originates from the crystallographic preferred orientation of highly anisotropic hydrous minerals (serpentine and talc) formed along steeply dipping faults and from the larger- scale vertical layering consisting of dry and hydrated crust - mantle sections whose spacing is several times smaller than teleseismic wavelengths. Fault orientations and estimated delay times are consistent with the observed shear- wave splitting patterns in most subduction zones