In vivo direct molecular imaging of early tumorigenesis and malignant progression induced by transgenic Expression of GFP-Met

Sharon Moshitch-Moshkovitz, Galia Tsarfaty, Dafna W. Kaufman, Gideon Y. Stein, Keren Shichrur, Eddy Solomon, Robert H. Sigler, James H. Resau, George F. Vande Woude, Ilan Tsarfaty

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)353-363
Number of pages11
JournalNeoplasia
Volume8
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Confocal intravital molecular imaging
  • GFP transgenic mice
  • Met hepatocyte growth factor/scatter factor
  • Receptor tyrosine kinase
  • Sebaceous gland tumor

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