PMID- 19825800
OWN - NLM
STAT- MEDLINE
DCOM- 20100112
LR  - 20200930
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 8
IP  - 10
DP  - 2009 Oct
TI  - Therapeutic potential of hepatocyte growth factor/scatter factor neutralizing 
      antibodies: inhibition of tumor growth in both autocrine and paracrine hepatocyte 
      growth factor/scatter factor:c-Met-driven models of leiomyosarcoma.
PG  - 2803-10
LID - 10.1158/1535-7163.MCT-09-0125 [doi]
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, have 
      been implicated in the growth and progression of a variety of solid human tumors. 
      Thus, inhibiting HGF/SF:c-Met signaling may provide a novel therapeutic approach 
      for treating human tumors. We have generated and characterized fully human 
      monoclonal antibodies that bind to and neutralize human HGF/SF. In this study, we 
      tested the effects of the investigational, human anti-human HGF/SF monoclonal 
      antibody, AMG 102, and a mixture of mouse anti-human HGF/SF monoclonal antibodies 
      (Amix) on HGF/SF-mediated cell migration, proliferation, and invasion in vitro. 
      Both agents had high HGF/SF-neutralizing activity in these cell-based assays. The 
      HGF/SF:c-Met pathway has been implicated in the growth of sarcomas; thus, we also 
      investigated the effect of AMG 102 on the growth of human leiomyosarcoma 
      (SK-LMS-1) in HGF/SF transgenic C3H severe combined immunodeficient mice 
      engineered to express high levels of human HGF/SF, as well as tumor growth of an 
      autocrine variant of the SK-LMS-1 cell line (SK-LMS-1TO) in nude mice. The 
      results indicate that interrupting autocrine and/or paracrine HGF/SF:c-Met 
      signaling with AMG 102 has profound antitumor effects. These findings suggest 
      that blocking HGF/SF:c-Met signaling may provide a potent intervention strategy 
      to treat patients with HGF/SF:c-Met-dependent tumors.
FAU - Gao, Chong-Feng
AU  - Gao CF
AD  - Laboratory of Molecular Oncology, Van Andel Research Institute, 333 Bostwick, 
      Northeast, Grand Rapids, MI 49503, USA.
FAU - Xie, Qian
AU  - Xie Q
FAU - Zhang, Yu-Wen
AU  - Zhang YW
FAU - Su, Yanli
AU  - Su Y
FAU - Zhao, Ping
AU  - Zhao P
FAU - Cao, Brian
AU  - Cao B
FAU - Furge, Kyle
AU  - Furge K
FAU - Sun, Jan
AU  - Sun J
FAU - Rex, Karen
AU  - Rex K
FAU - Osgood, Tao
AU  - Osgood T
FAU - Coxon, Angela
AU  - Coxon A
FAU - Burgess, Teresa L
AU  - Burgess TL
FAU - Vande Woude, George F
AU  - Vande Woude GF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Ligands)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing/pharmacology/*therapeutic use
MH  - *Autocrine Communication/drug effects
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Fibrinolysin/metabolism
MH  - Hepatocyte Growth Factor/*immunology
MH  - Humans
MH  - Leiomyosarcoma/*drug therapy/immunology/*pathology
MH  - Ligands
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Immunological
MH  - Neoplasm Invasiveness
MH  - *Paracrine Communication/drug effects
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Signal Transduction/drug effects
MH  - Urokinase-Type Plasminogen Activator/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2009/10/15 06:00
MHDA- 2010/01/13 06:00
CRDT- 2009/10/15 06:00
PHST- 2009/10/15 06:00 [entrez]
PHST- 2009/10/15 06:00 [pubmed]
PHST- 2010/01/13 06:00 [medline]
AID - 8/10/2803 [pii]
AID - 10.1158/1535-7163.MCT-09-0125 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2009 Oct;8(10):2803-10. doi: 10.1158/1535-7163.MCT-09-0125.