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Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
MET overexpression turns human primary osteoblasts into osteosarcomas
Salvatore Patanè1, Sofia Avnet, Nadia Coltella
1Laboratory of Cancer Genetics, University of Turin School of Medicine, Candiolo (Turin), Italy.
Cancer Research
|May 3, 2006
Summary
Overexpression of the MET oncogene transforms human osteoblasts into osteosarcoma cells, demonstrating MET
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The MET oncogene plays a role in papillary renal cell carcinoma pathogenesis via activating mutations.
- MET amplification/overexpression occurs in various sporadic tumors, including osteosarcoma.
Purpose of the Study:
- To investigate the oncogenic potential of MET overexpression in osteoblasts.
- To determine if MET overexpression is sufficient to induce osteosarcoma.
Main Methods:
- Lentiviral vector-mediated gene transfer to overexpress MET in primary human osteoblasts.
- In vitro and in vivo analysis of transformed osteoblasts.
- Gene silencing using short-hairpin RNA and dominant-negative MET receptor to inhibit MET signaling.
Main Results:
- MET overexpression converted human osteoblasts into osteosarcoma cells with transformed phenotypes in vitro.
- In vivo studies showed osteosarcoma features, including atypical nuclei, aberrant mitoses, osteoid secretion, and neovascularization.
- Inhibition of MET expression or signaling fully abrogated transformation and tumorigenesis.
Conclusions:
- MET overexpression is oncogenic and sufficient to drive osteosarcoma development.
- MET is essential for maintaining the osteosarcoma cancer phenotype.
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