PMID- 10066093
OWN - NLM
STAT- MEDLINE
DCOM- 19990427
LR  - 20190909
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 40
IP  - 3
DP  - 1998 Dec
TI  - Urokinase induces receptor mediated brain tumor cell migration and invasion.
PG  - 215-26
AB  - The plasminogen activation (PA) system plays an important role in tumor invasion 
      by initiating pericellular proteolysis of the extracellular matrix (ECM) and 
      inducing cell migration. Malignant brain tumors overexpress PA members and 
      characteristically invade by migrating on ECM-producing white matter tracts and 
      blood vessel walls. To determine whether urokinase-type plasminogen activator 
      (uPA) and its receptor (uPAR) directly modulate the migration of brain tumor 
      cells, we examined six human brain tumor cell lines, 2 astrocytomas (SW1088, 
      SW1783), 2 medullobastomas (Daoy, D341Med), and 2 glioblastomas (U87MG, U118MG), 
      for their surface uPAR expression, endogenous PA activity, and functional 
      proteolytic activity by an ECM-degradation assay. Migration on Transwell 
      membranes and invasion of Matrigel was then tested by pre-incubating the cells 
      with increasing concentrations of either uPA, the proteolytically inactive 
      amino-terminal fragment (ATF) of uPA, or the uPAR cleaving enzyme, 
      phosphatidylinositol-specific phospholipase C (PI-PLC). All of the cell lines, 
      except D341Med, express surface uPAR protein and uPA activity. High levels of 
      uPAR and uPA activity correlated with cellular degradation of ECM, cell 
      migration, and Matrigel invasion. Cell migration and invasion were enhanced by 
      uPA or ATF in a dose dependent manner, while PI-PLC treatment abolished the uPA 
      effect and inhibited migration and invasion. We conclude that ligation of uPAR by 
      uPA directly induces brain tumor cell migration, independent of uPA-mediated 
      proteolysis; and in concert with ECM degradation, markedly enhances invasion. 
      Conversely, removing membrane bound uPAR from the surface of the cells studied 
      inhibited their ability to migrate and invade even in the presence of 
      proteolytically active uPA.
FAU - MacDonald, T J
AU  - MacDonald TJ
AD  - Department of Pediatrics, Childrens Hospital Los Angeles University of Southern 
      California School of Medicine, 90027, USA.
FAU - DeClerck, Y A
AU  - DeClerck YA
FAU - Laug, W E
AU  - Laug WE
LA  - eng
GR  - T32CA09659/CA/NCI 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  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (PLAUR protein, human)
RN  - 0 (Proteoglycans)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Brain Neoplasms/metabolism/*pathology/*physiopathology
MH  - Cell Movement/drug effects/physiology
MH  - Collagen
MH  - Drug Combinations
MH  - Extracellular Matrix/metabolism
MH  - Humans
MH  - Laminin
MH  - Neoplasm Invasiveness/*physiopathology
MH  - Proteoglycans
MH  - Receptors, Cell Surface/*physiology
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/*pharmacology
EDAT- 1999/03/05 00:00
MHDA- 1999/03/05 00:01
CRDT- 1999/03/05 00:00
PHST- 1999/03/05 00:00 [pubmed]
PHST- 1999/03/05 00:01 [medline]
PHST- 1999/03/05 00:00 [entrez]
AID - 10.1023/a:1006150506789 [doi]
PST - ppublish
SO  - J Neurooncol. 1998 Dec;40(3):215-26. doi: 10.1023/a:1006150506789.