PMID- 8622656
OWN - NLM
STAT- MEDLINE
DCOM- 19960618
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 16
IP  - 3
DP  - 1996 Mar
TI  - Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth 
      factor/scatter factor-met signalling in human cells concomitant with induction of 
      the urokinase proteolysis network.
PG  - 1115-25
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector of 
      cells expressing the Met tyrosine kinase receptor. Although HGF/SF is synthesized 
      by mesenchymal cells and acts predominantly on epithelial cells, we have recently 
      demonstrated that human sarcoma cell lines often inappropriately express high 
      levels of Met and respond mitogenically to HGF/SF. In the present report we show 
      that HGF/SF-Met signalling in the human leiomyosarcoma cell line SK-LMS-1 
      enhances its in vivo tumorigenicity, an effect for which the mitogenicity of this 
      signalling pathway is likely to play a role. In addition, we found that 
      HGF/SF-Met signalling dramatically induces the in vitro invasiveness and in vivo 
      metastatic potential of these cells. We have studied the molecular basis by which 
      HGFSF-Met signalling mediates the invasive phenotype. A strong correlation has 
      previously been demonstrated between the activation of the urokinase plasminogen 
      activator (uPA) proteolysis network and the acquisition of the 
      invasive-metastatic phenotype, and we show here that HGF/SF-Met signalling 
      significantly increases the protein levels of both uPA and its cellular receptor 
      in SK-LMS-1 cells. This results in elevated levels of cell-associated uPA and 
      enhanced plasmin-generating ability by these cells. These studies couple 
      HGF/SF-Met signalling to the activation of proteases that mediate dissolution of 
      the extracellular matrix-basement membrane, and important property for cellular 
      invasion-metastasis.
FAU - Jeffers, M
AU  - Jeffers M
AD  - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, 
      Maryland 21702, USA.
FAU - Rong, S
AU  - Rong S
FAU - Vande Woude, G F
AU  - Vande Woude GF
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - Cell Movement
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Leiomyosarcoma/*metabolism/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/*metabolism
PMC - PMC231094
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
PMCR- 1996/03/01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
PHST- 1996/03/01 00:00 [pmc-release]
AID - 10.1128/MCB.16.3.1115 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1996 Mar;16(3):1115-25. doi: 10.1128/MCB.16.3.1115.