PMID- 11410166
OWN - NLM
STAT- MEDLINE
DCOM- 20010712
LR  - 20081121
IS  - 1044-5498 (Print)
IS  - 1044-5498 (Linking)
VI  - 20
IP  - 5
DP  - 2001 May
TI  - cDNA transfection of amino-terminal fragment of urokinase efficiently inhibits 
      cancer cell invasion and metastasis.
PG  - 297-305
AB  - Focusing of urokinase-type plasminogen activator (uPA) to the cell surface via 
      binding to its specific receptor (uPAR, CD87) is critical for tumor invasion and 
      metastasis. Consequently, the inhibition of uPA-uPAR interaction on the cell 
      surface might be a promising anti-invasion and anti-metastasis strategy. We 
      examined the effects of cDNA transfection of the human uPA amino-terminal 
      fragment (ATF) on invasion and metastasis of cancer cells. First, a highly 
      metastatic human lung giant-cell carcinoma cell line (PG), used as the target 
      cell for evaluation of this effect, was demonstrated to express both uPA and 
      uPAR. Then, ATF, which contains an intact uPAR binding site but is catalytically 
      inactive, was designed as an antagonist of uPA-uPAR interaction and was 
      transfected into PG cells. [(3)H]-Thymidine incorporation and cell growth curves 
      indicated that expressed ATF did not affect the proliferation of transfected 
      cells. However, analysis by scanning electron microscopy revealed that ATF 
      changed the host cells from the typical invasive phenotype to a noninvasive one. 
      Correspondingly, the modified Boyden chamber test in vitro showed that ATF 
      expression significantly decreased the invasive capacity of transfected cells. 
      Furthermore, in the spontaneous metastasis model, it was confirmed in vivo that 
      expressed ATF remarkably inhibited lung metastasis of implanted ATF-transfected 
      PG cells. In summary, autocrine ATF could act as an antagonist of uPA-uPAR 
      interaction, and ATF cDNA transfection could efficiently inhibit the invasion and 
      metastasis of the cancer cells. Inhibition of uPA-uPAR interaction on the cell 
      surface might be a promising anti-invasion and anti-metastasis strategy.
FAU - Zhu, F
AU  - Zhu F
AD  - Beijing Institute of Radiation Medicine, Beijing, China.
FAU - Jia, S
AU  - Jia S
FAU - Xing, G
AU  - Xing G
FAU - Gao, L
AU  - Gao L
FAU - Zhang, L
AU  - Zhang L
FAU - He, F
AU  - He F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - DNA Cell Biol
JT  - DNA and cell biology
JID - 9004522
RN  - 0 (DNA, Complementary)
RN  - 0 (PLAUR protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Plaur protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - Cell Size
MH  - DNA, Complementary
MH  - Humans
MH  - Immunoblotting
MH  - Lung Neoplasms
MH  - Mice
MH  - Mice, Nude
MH  - *Neoplasm Invasiveness
MH  - *Neoplasm Metastasis
MH  - Peptide Fragments/chemistry/genetics/*metabolism
MH  - Plasminogen Activators/chemistry/genetics/*metabolism
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transfection
MH  - Transplants
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/chemistry/genetics/*metabolism
EDAT- 2001/06/19 10:00
MHDA- 2001/07/13 10:01
CRDT- 2001/06/19 10:00
PHST- 2001/06/19 10:00 [pubmed]
PHST- 2001/07/13 10:01 [medline]
PHST- 2001/06/19 10:00 [entrez]
AID - 10.1089/104454901750232490 [doi]
PST - ppublish
SO  - DNA Cell Biol. 2001 May;20(5):297-305. doi: 10.1089/104454901750232490.