PMID- 11416216
OWN - NLM
STAT- MEDLINE
DCOM- 20010726
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 13
DP  - 2001 Jun 19
TI  - Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor 
      (HGF/SF) display antitumor activity in animal models.
PG  - 7443-8
AB  - The hepatocyte growth factor (HGF/SF) receptor, Met, regulates mitogenesis, 
      motility, and morphogenesis in a cell type-dependent fashion. Activation of Met 
      via autocrine, paracrine, or mutational mechanisms can lead to tumorigenesis and 
      metastasis and numerous studies have linked inappropriate expression of this 
      ligand-receptor pair to most types of human solid tumors. To prepare mAbs to 
      human HGF/SF, mice were immunized with native and denatured preparations of the 
      ligand. Recloned mAbs were tested in vitro for blocking activity against 
      scattering and branching morphogenesis. Our results show that no single mAb was 
      capable of neutralizing the in vitro activity of HGF/SF, and that the ligand 
      possesses a minimum of three epitopes that must be blocked to prevent Met 
      tyrosine kinase activation. In vivo, the neutralizing mAb combination inhibited 
      s.c. growth in athymic nu/nu mice of tumors dependent on an autocrine Met-HGF/SF 
      loop. Importantly, growth of human glioblastoma multiforme xenografts expressing 
      Met and HGF/SF were markedly reduced in the presence of HGF/SF-neutralizing mAbs. 
      These results suggest interrupting autocrine and/or paracrine Met-HGF/SF 
      signaling in tumors dependent on this pathway is a possible intervention 
      strategy.
FAU - Cao, B
AU  - Cao B
AD  - Van Andel Research Institute, 333 Bostwick, N.E., Grand Rapids, MI 49503, USA.
FAU - Su, Y
AU  - Su Y
FAU - Oskarsson, M
AU  - Oskarsson M
FAU - Zhao, P
AU  - Zhao P
FAU - Kort, E J
AU  - Kort EJ
FAU - Fisher, R J
AU  - Fisher RJ
FAU - Wang, L M
AU  - Wang LM
FAU - Vande Woude, G F
AU  - Vande Woude GF
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Line
MH  - Dogs
MH  - Female
MH  - Glioblastoma/pathology/*therapy
MH  - Hepatocyte Growth Factor/genetics/*immunology
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Morphogenesis
MH  - Neutralization Tests
MH  - Proto-Oncogene Proteins c-met/genetics/metabolism
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
PMC - PMC34688
EDAT- 2001/06/21 10:00
MHDA- 2001/07/28 10:01
PMCR- 2001/12/19
CRDT- 2001/06/21 10:00
PHST- 2001/06/21 10:00 [pubmed]
PHST- 2001/07/28 10:01 [medline]
PHST- 2001/06/21 10:00 [entrez]
PHST- 2001/12/19 00:00 [pmc-release]
AID - 98/13/7443 [pii]
AID - 131200498 [pii]
AID - 2004 [pii]
AID - 10.1073/pnas.131200498 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7443-8. doi: 10.1073/pnas.131200498.