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The Met proto-oncogene mesenchymal to epithelial cell conversion
I Tsarfaty1, S Rong, J H Resau
1ABL-Basic Research Program, National Cancer Institute (NCI)-Frederick Cancer Research and Development Center, MD 21702-1201.
Science (New York, N.Y.)
|January 7, 1994
Summary
Coexpressing the Met receptor and hepatocyte growth factor/scatter factor (HGF/SF) induced tumorigenicity in fibroblasts. Tumors showed epithelial and mesenchymal markers, mimicking embryonic development and suggesting a role for Met-HGF/SF signaling in both processes.
Area of Science:
- Cell biology
- Molecular oncology
- Developmental biology
Background:
- The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), are crucial for embryonic development.
- Dysregulation of Met-HGF/SF signaling is implicated in various human cancers.
- Understanding the role of Met-HGF/SF in cellular transformation is essential for cancer research.
Purpose of the Study:
- To investigate the role of Met-HGF/SF coexpression in cellular tumorigenicity.
- To characterize the morphological and molecular features of tumors formed by Met-HGF/SF expressing cells.
- To explore the potential link between Met-HGF/SF signaling and developmental processes.
Main Methods:
- Coexpression of human Met receptor and HGF/SF in NIH 3T3 fibroblasts.
- Tumorigenicity assays in nude mice.
- Histological and immunohistochemical analysis of resultant tumors.
- Assessment of cytoskeletal markers (cytokeratin, vimentin) and junctional proteins.
Main Results:
- Coexpression of Met and HGF/SF rendered NIH 3T3 fibroblasts tumorigenic in vivo.
- Tumors exhibited lumen-like morphology and contained carcinoma-like areas with desmosome-like junctions.
- Tumor cells displayed coexpression of epithelial (cytokeratin) and mesenchymal (vimentin) markers.
- Enhanced expression of desmosomal and tight-junction proteins was observed in tumor cells.
Conclusions:
- Met-HGF/SF signaling can induce tumorigenicity and a mesenchymal-to-epithelial transition phenotype.
- The observed cellular conversion in tumors mimics processes seen during embryonic kidney development.
- Met-HGF/SF signaling likely plays a role in both tumorigenesis and embryonic development, particularly in contexts involving epithelial-mesenchymal plasticity.