PMID- 16790084
OWN - NLM
STAT- MEDLINE
DCOM- 20060831
LR  - 20181113
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 8
IP  - 5
DP  - 2006 May
TI  - In vivo direct molecular imaging of early tumorigenesis and malignant progression 
      induced by transgenic expression of GFP-Met.
PG  - 353-63
AB  - The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor/scatter 
      factor (HGF/SF), play an important role in normal developmental processes, as 
      well as in tumorigenicity and metastasis. We constructed a green fluorescent 
      protein (GFP) Met chimeric molecule that functions similarly to the wild-type Met 
      receptor and generated GFP-Met transgenic mice. These mice ubiquitously expressed 
      GFP-Met in specific epithelial and endothelial cells and displayed enhanced 
      GFP-Met fluorescence in sebaceous glands. Thirty-two percent of males 
      spontaneously developed adenomas, adenocarcinomas, and angiosarcomas in their 
      lower abdominal sebaceous glands. Approximately 70% of adenocarcinoma tumors 
      metastasized to the kidneys, lungs, or liver. Quantitative subcellular-resolution 
      intravital imaging revealed very high levels of GFP-Met in tumor lesions and in 
      single isolated cells surrounding them, relative to normal sebaceous glands. 
      These single cells preceded the formation of local and distal metastases. Higher 
      GFP-Met levels correlated with earlier tumor onset and aggressiveness, further 
      demonstrating the role of Met-HGF/SF signaling in cellular transformation and 
      acquisition of invasive and metastatic phenotypes. Our novel mouse model and 
      high-resolution intravital molecular imaging create a powerful tool that enables 
      direct real-time molecular imaging of receptor expression and localization during 
      primary events of tumorigenicity and metastasis at single-cell resolution.
FAU - Moshitch-Moshkovitz, Sharon
AU  - Moshitch-Moshkovitz S
AD  - Van Andel Research Institute, Grand Rapids, MI 49503, USA.
FAU - Tsarfaty, Galia
AU  - Tsarfaty G
FAU - Kaufman, Dafna W
AU  - Kaufman DW
FAU - Stein, Gideon Y
AU  - Stein GY
FAU - Shichrur, Keren
AU  - Shichrur K
FAU - Solomon, Eddy
AU  - Solomon E
FAU - Sigler, Robert H
AU  - Sigler RH
FAU - Resau, James H
AU  - Resau JH
FAU - Vande Woude, George F
AU  - Vande Woude GF
FAU - Tsarfaty, Ilan
AU  - Tsarfaty I
LA  - eng
GR  - P50 CA093990/CA/NCI NIH HHS/United States
GR  - P50CA93990/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Diagnostic Imaging/instrumentation/*methods
MH  - Disease Progression
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Green Fluorescent Proteins/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence/*methods
MH  - Neoplasm Metastasis
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - *Transgenes
PMC - PMC1592452
EDAT- 2006/06/23 09:00
MHDA- 2006/09/01 09:00
PMCR- 2006/05/01
CRDT- 2006/06/23 09:00
PHST- 2006/06/23 09:00 [pubmed]
PHST- 2006/09/01 09:00 [medline]
PHST- 2006/06/23 09:00 [entrez]
PHST- 2006/05/01 00:00 [pmc-release]
AID - 05634 [pii]
AID - 10.1593/neo.05634 [doi]
PST - ppublish
SO  - Neoplasia. 2006 May;8(5):353-63. doi: 10.1593/neo.05634.