PMID- 12420219
OWN - NLM
STAT- MEDLINE
DCOM- 20021212
LR  - 20121115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 21
IP  - 51
DP  - 2002 Nov 7
TI  - Modulation of invasive properties of human glioblastoma cells stably expressing 
      amino-terminal fragment of urokinase-type plasminogen activator.
PG  - 7824-30
AB  - The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) 
      on the surface of tumor cells is involved in the activation of proteolytic 
      cascades responsible for the invasiveness of those cells. The diffuse, extensive 
      infiltration of glioblastomas into the surrounding normal brain tissue is 
      believed to rely on modifications of the proteolysis of extracellular matrix 
      components; blocking the interaction between uPA and uPAR might be a suitable 
      approach for inhibiting glioma tumorigenesis. We assessed how expression of an 
      amino-terminal fragment (ATF) of uPA that contains binding site to uPAR affects 
      the invasiveness of SNB19 human glioblastoma cells. SNB19 cells were transfected 
      with an expression plasmid (pcDNA3-ATF) containing a cDNA sequence of ATF-uPA. 
      The resulting ATF-uPA-expressing clones showed markedly less cell adhesion, 
      spreading, and clonogenicity than did control cells. Endogenous ATF expression 
      also significantly decreased the invasive capacity of transfected glioblastoma 
      cells in Matrigel and spheroid-rat brain cell aggregate models. ATF-uPA 
      transfectants were also markedly less invasive than parental SNB19 cells after 
      injection into the brains of nude mice, suggesting that competitive inhibition of 
      the uPA-uPAR interaction on SNB19 cells by means of transfection with ATF cDNA 
      could be a useful therapeutic strategy for inhibiting tumor progression.
FAU - Mohanam, Sanjeeva
AU  - Mohanam S
AD  - Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, 
      University of Illinois College of Medicine at Peoria, Peoria, Illinois 
      61656-1649, USA.
FAU - Chandrasekar, Nirmala
AU  - Chandrasekar N
FAU - Yanamandra, Niranjan
AU  - Yanamandra N
FAU - Khawar, Siddique
AU  - Khawar S
FAU - Mirza, Faiz
AU  - Mirza F
FAU - Dinh, Dzung H
AU  - Dinh DH
FAU - Olivero, William C
AU  - Olivero WC
FAU - Rao, Jasti S
AU  - Rao JS
LA  - eng
GR  - CA75557/CA/NCI NIH HHS/United States
GR  - CA76350/CA/NCI NIH HHS/United States
GR  - CA85216/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Actins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PLAUR protein, human)
RN  - 0 (Plaur protein, mouse)
RN  - 0 (Plaur protein, rat)
RN  - 0 (Proteoglycans)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Binding Sites
MH  - Brain Neoplasms/enzymology/*pathology/therapy
MH  - Cell Adhesion
MH  - Cell Aggregation
MH  - Clone Cells/pathology
MH  - Collagen
MH  - Cytoskeleton/ultrastructure
MH  - DNA, Complementary/genetics
MH  - Drug Combinations
MH  - Genetic Therapy
MH  - Glioblastoma/enzymology/*pathology/therapy
MH  - Humans
MH  - Laminin
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Invasiveness/*physiopathology
MH  - Neoplasm Proteins/chemistry/genetics/*physiology
MH  - Protein Structure, Tertiary
MH  - Proteoglycans
MH  - Rats
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Recombinant Fusion Proteins/physiology
MH  - Spheroids, Cellular/pathology
MH  - Structure-Activity Relationship
MH  - Transfection
MH  - Tumor Cells, Cultured/pathology
MH  - Tumor Stem Cell Assay
MH  - Urokinase-Type Plasminogen Activator/chemistry/genetics/*physiology
MH  - Xenograft Model Antitumor Assays
EDAT- 2002/11/07 04:00
MHDA- 2002/12/13 04:00
CRDT- 2002/11/07 04:00
PHST- 2002/05/08 00:00 [received]
PHST- 2002/07/12 00:00 [revised]
PHST- 2002/07/18 00:00 [accepted]
PHST- 2002/11/07 04:00 [pubmed]
PHST- 2002/12/13 04:00 [medline]
PHST- 2002/11/07 04:00 [entrez]
AID - 10.1038/sj.onc.1205893 [doi]
PST - ppublish
SO  - Oncogene. 2002 Nov 7;21(51):7824-30. doi: 10.1038/sj.onc.1205893.