In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558606800552 |
| _version_ | 1819041528695226368 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sharon Moshitch-Moshkovitz |
| collection | DOAJ |
| description | 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 subcellularresolution 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 realtime molecular imaging of receptor expression and localization during primary events of tumorigenicity and metastasis at single-cell resolution. |
| first_indexed | 2024-12-21T09:26:26Z |
| format | Article |
| id | doaj.art-6655673b43f14144aa7c6b9debe68288 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T09:26:26Z |
| publishDate | 2006-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-6655673b43f14144aa7c6b9debe682882022-12-21T19:08:52ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022006-05-018535336310.1593/neo.05634In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-MetSharon Moshitch-Moshkovitz0Galia Tsarfaty1Dafna W. Kaufman2Gideon Y. Stein3Keren Shichrur4Eddy Solomon5Robert H. Sigler6James H. Resau7George F. Vande Woude8Ilan Tsarfaty9Van Andel Research Institute, Grand Rapids, MI 49503, USAVan Andel Research Institute, Grand Rapids, MI 49503, USAVan Andel Research Institute, Grand Rapids, MI 49503, USADepartment of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelDepartment of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelDepartment of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelVan Andel Research Institute, Grand Rapids, MI 49503, USAVan Andel Research Institute, Grand Rapids, MI 49503, USAVan Andel Research Institute, Grand Rapids, MI 49503, USAVan Andel Research Institute, Grand Rapids, MI 49503, USAThe 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 subcellularresolution 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 realtime molecular imaging of receptor expression and localization during primary events of tumorigenicity and metastasis at single-cell resolution.http://www.sciencedirect.com/science/article/pii/S1476558606800552Receptor tyrosine kinaseMet hepatocyte growth factor/scatter factorsebaceous gland tumorconfocal intravital molecular imagingGFP transgenic mice |
| spellingShingle | 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 In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met Neoplasia: An International Journal for Oncology Research Receptor tyrosine kinase Met hepatocyte growth factor/scatter factor sebaceous gland tumor confocal intravital molecular imaging GFP transgenic mice |
| title | In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met |
| title_full | In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met |
| title_fullStr | In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met |
| title_full_unstemmed | In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met |
| title_short | In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met |
| title_sort | in vivo direct molecular imaging of early tumorigenesis and malignant progression induced by transgenic expression of gfp met |
| topic | Receptor tyrosine kinase Met hepatocyte growth factor/scatter factor sebaceous gland tumor confocal intravital molecular imaging GFP transgenic mice |
| url | http://www.sciencedirect.com/science/article/pii/S1476558606800552 |
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