PMID- 7611439
OWN - NLM
STAT- MEDLINE
DCOM- 19950815
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 268
IP  - 6 Pt 1
DP  - 1995 Jun
TI  - Urokinase receptor in human malignant mesothelioma cells: role in tumor cell 
      mitogenesis and proteolysis.
PG  - L972-82
AB  - Urokinase (uPA) interacts with its receptor (uPAR) to promote proteolysis and 
      tumor migration, functions of potential importance in the pathogenesis of 
      malignant mesothelioma. Immunohistochemistry of human malignant mesothelioma 
      tissue and mesothelioma cells (MS-1) showed that mesothelioma cells express uPAR. 
      We isolated uPAR from MS-1 cells by metabolic labeling and showed that it could 
      be induced by phorbol myristate acetate (PMA), lipopolysaccharide (LPS), a 
      transforming growth factor-beta (TGF-beta) or tumor necrosis factor-alpha 
      (TNF-alpha). Experiments with MS-1 cells showed that uPA binding was saturable, 
      specific, and reversible with a mean dissociation constant (Kd) of 5.4 +/- 1.1 
      nM. Binding was inhibited by a blocking antibody to uPAR and by the uPA 
      amino-terminal fragment (ATF), but not by low molecular weight uPA. uPAR 
      expression was regulated transcriptionally and translationally; antisense 
      oligonucleotides blocked expression of uPAR protein. Plasminogen activator 
      inhibitor-1 (PAI-1) inhibited PA activity of preformed uPA/uPAR complexes and 
      increased cycling of the receptor from the cell surface. Stimulation of 
      subconfluent MS-1 cells by high molecular weight or recombinant uPA, but not ATF 
      or low molecular weight fragment, caused concentration-dependent incorporation of 
      [3H]thymidine. These data indicate a novel mechanism by which malignant 
      mesothelioma cells localize pericellular proteolysis and concurrently regulate 
      tumor cell proliferation.
FAU - Shetty, S
AU  - Shetty S
AD  - Department of Medicine, University of Texas Health Science Center at Tyler 75710, 
      USA.
FAU - Kumar, A
AU  - Kumar A
FAU - Johnson, A
AU  - Johnson A
FAU - Pueblitz, S
AU  - Pueblitz S
FAU - Idell, S
AU  - Idell S
LA  - eng
GR  - HL-37770/HL/NHLBI NIH HHS/United States
GR  - HL-45018/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (PLAUR protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - AE28F7PNPL (Methionine)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Cell Cycle
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Immunohistochemistry
MH  - Iodine Radioisotopes
MH  - Kinetics
MH  - Mesothelioma/*metabolism/*pathology
MH  - Methionine/metabolism
MH  - Protein Biosynthesis
MH  - RNA, Messenger/analysis
MH  - Receptors, Cell Surface/biosynthesis/*metabolism
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Recombinant Proteins/metabolism/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thymidine/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Transforming Growth Factor beta/pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Urokinase-Type Plasminogen Activator/metabolism/pharmacology
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
AID - 10.1152/ajplung.1995.268.6.L972 [doi]
PST - ppublish
SO  - Am J Physiol. 1995 Jun;268(6 Pt 1):L972-82. doi: 10.1152/ajplung.1995.268.6.L972.