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Updated: Jun 23, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
met oncogene activation qualifies spontaneous canine osteosarcoma as a suitable pre-clinical model of human
Raffaella De Maria1, Silvia Miretti, Selina Iussich
1Department of Animal Pathology, University of Torino, Grugliasco, Turin, Italy.
Abstract:
The Met receptor tyrosine kinase (RTK) is aberrantly expressed in human osteosarcoma and is an attractive molecular target for cancer therapy. We studied spontaneous canine osteosarcoma (OSA) as a potential pre-clinical model for evaluation of Met-targeted therapies. The canine MET oncogene exhibits 90% homology compared with human MET, indicating that cross-species functional studies are a viable strategy. Expression and activation of the canine Met receptor were studied utilizing immunohistochemical techniques in 39 samples of canine osteosarcoma, including 35 primary tumours and four metastases. Although the Met RTK is barely detectable in primary culture of canine osteoblasts, high expression of Met protein was observed in 80% of canine osteosarcoma samples acquired from various breeds. Met protein overexpression was also concordant with its activation as indicated by phosphorylation of critical tyrosine residues. In addition, Met was expressed and constitutively activated in canine osteosarcoma cell lines. OSA cells expressing high levels of Met demonstrated activation of downstream transducers, elevated spontaneous motility, and invasiveness which were impaired by both a small molecule inhibitor of Met catalytic activity (PHA-665752) and met-specific, stable RNA interference obtained by means of lentiviral vector. Similar to observations in human OSA, these data suggest that Met is commonly overexpressed and activated in canine OSA and that inhibition of Met impairs the invasive and motogenic properties of canine OSA cells. These data implicate Met as a potentially important factor for canine OSA progression and indicate that it represents a viable model to study Met-targeted therapies.
Insights
Canine osteosarcoma (OSA) commonly overexpresses and activates the Met receptor tyrosine kinase (RTK). Inhibiting Met reduces OSA cell motility and invasiveness, supporting its role in cancer progression and Met-targeted therapy evaluation.
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- Met receptor tyrosine kinase (RTK) is a target in human osteosarcoma (OSA).
- Canine OSA serves as a preclinical model for evaluating Met-targeted therapies due to high homology with human MET.
- Investigating Met's role in canine OSA progression is crucial for therapeutic development.
Purpose of the Study:
- To investigate the expression and activation of the Met receptor in canine osteosarcoma (OSA).
- To evaluate the efficacy of Met inhibition on canine OSA cell behavior.
- To establish canine OSA as a relevant model for Met-targeted cancer therapy studies.
Main Methods:
- Immunohistochemical analysis of Met expression and activation in 39 canine OSA samples.
- Assessment of Met downstream signaling, motility, and invasiveness in canine OSA cell lines.
- Treatment of OSA cells with a Met inhibitor (PHA-665752) and lentiviral-mediated RNA interference targeting Met.
Main Results:
- High Met protein expression and activation (phosphorylation) observed in 80% of canine OSA samples.
- Met overexpression and constitutive activation were confirmed in canine OSA cell lines.
- Inhibition of Met significantly impaired spontaneous motility and invasiveness of OSA cells.
Conclusions:
- Met is frequently overexpressed and activated in canine osteosarcoma.
- Targeting Met effectively reduces the invasive and motogenic properties of canine OSA cells.
- Canine OSA is a valuable model for studying Met-targeted therapies in osteosarcoma.
