PMID- 15531925
OWN - NLM
STAT- MEDLINE
DCOM- 20050217
LR  - 20220317
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 1
DP  - 2005 Jan 6
TI  - Enhanced growth of human met-expressing xenografts in a new strain of 
      immunocompromised mice transgenic for human hepatocyte growth factor/scatter 
      factor.
PG  - 101-6
AB  - Downstream signaling that results from the interaction of hepatocyte growth 
      factor/scatter factor (HGF/SF) with the receptor tyrosine kinase Met plays 
      critical roles in tumor development, progression, and metastasis. This 
      ligand-receptor pair is an attractive target for new diagnostic and therapeutic 
      agents, preclinical development of which requires suitable animal models. The 
      growth of heterotopic and orthotopic Met-expressing human tumor xenografts in 
      conventional strains of immunocompromised mice inadequately replicates the 
      paracrine stimulation by human HGF/SF (hHGF/SF) that occurs in humans with 
      cancer. We have therefore generated a mouse strain transgenic for hHGF/SF 
      (designated hHGF-Tg) on a severe combined immunodeficiency (SCID) background. We 
      report here that the presence of ectopically expressed hHGF/SF ligand 
      significantly enhances growth of heterotopic subcutaneous xenografts derived from 
      human Met-expressing cancer cells, including the lines SK-LMS-1 (human 
      leiomyosarcoma), U118 (human glioblastoma), and DU145 (human prostate carcinoma), 
      but not that of M14-Mel xenografts (human melanoma that expresses insignificant 
      levels of Met). Our results indicate that ectopic hHGF/SF can specifically 
      activate Met in human tumor xenografts. This new hHGF-Tg strain of mice should 
      provide a powerful tool for evaluating drugs and diagnostic agents that target 
      the various pathways influenced by Met activity.
FAU - Zhang, Yu-Wen
AU  - Zhang YW
AD  - Laboratory of Molecular Oncology, Van Andel Research Institute, 333 Bostwick 
      Avenue NE, Grand Rapids, MI 49503, USA.
FAU - Su, Yanli
AU  - Su Y
FAU - Lanning, Nathan
AU  - Lanning N
FAU - Gustafson, Margaret
AU  - Gustafson M
FAU - Shinomiya, Nariyoshi
AU  - Shinomiya N
FAU - Zhao, Ping
AU  - Zhao P
FAU - Cao, Brian
AU  - Cao B
FAU - Tsarfaty, Galia
AU  - Tsarfaty G
FAU - Wang, Ling-Mei
AU  - Wang LM
FAU - Hay, Rick
AU  - Hay R
FAU - Vande Woude, George F
AU  - Vande Woude GF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Hepatocyte Growth Factor/genetics/*metabolism
MH  - Humans
MH  - Immunocompromised Host/immunology
MH  - Mice
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Receptors, Growth Factor/genetics/*metabolism
MH  - Time Factors
MH  - *Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 2004/11/09 09:00
MHDA- 2005/02/18 09:00
CRDT- 2004/11/09 09:00
PHST- 2004/11/09 09:00 [pubmed]
PHST- 2005/02/18 09:00 [medline]
PHST- 2004/11/09 09:00 [entrez]
AID - 1208181 [pii]
AID - 10.1038/sj.onc.1208181 [doi]
PST - ppublish
SO  - Oncogene. 2005 Jan 6;24(1):101-6. doi: 10.1038/sj.onc.1208181.