| First Author | Moshitch-Moshkovitz S | Year | 2006 |
| Journal | Neoplasia | Volume | 8 |
| Issue | 5 | Pages | 353-63 |
| PubMed ID | 16790084 | Mgi Jnum | J:114940 |
| Mgi Id | MGI:3690421 | Doi | 10.1593/neo.05634 |
| Citation | Moshitch-Moshkovitz S, et al. (2006) In vivo direct molecular imaging of early tumorigenesis and malignant progression induced by transgenic expression of GFP-Met. Neoplasia 8(5):353-63 |
| abstractText | 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. |
