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

Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print Cited Medium: Print ISSN: 0007-0920 (Print) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE

Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.

Gene Expression Regulation, Neoplastic/*drug effects ; Oxygen/*pharmacology ; Plasminogen Activator Inhibitor 1/*metabolism ; Receptors, Cell Surface/*metabolism ; Sarcoma/*metabolism ; Urokinase-Type Plasminogen Activator/*metabolism; Animals ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Profiling ; Hypoxia/metabolism ; Organ Specificity ; Oxygen/metabolism ; Plasminogen Activator Inhibitor 1/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats ; Receptors, Cell Surface/genetics ; Receptors, Urokinase Plasminogen Activator ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoma/genetics ; Sarcoma/pathology ; Tumor Cells, Cultured ; Urokinase-Type Plasminogen Activator/genetics

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.
(Copyright 2002 Cancer Research UK)

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0 (Plasminogen Activator Inhibitor 1)
0 (Plaur protein, rat)
0 (RNA, Messenger)
0 (Receptors, Cell Surface)
0 (Receptors, Urokinase Plasminogen Activator)
EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
S88TT14065 (Oxygen)

Date Created: 20020416 Date Completed: 20020524 Latest Revision: 20220317

20231215

PMC2375355

10.1038/sj.bjc.6600237

11953898