Related Experiment Video
Updated: Jun 20, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
A novel small molecule Met inhibitor, PF2362376, exhibits biological activity against osteosarcoma
A T Liao1, J McCleese, S Kamerling
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
The receptor tyrosine kinase Met is dysregulated in several human cancers including osteosarcoma (OSA) in which overexpression is a negative prognostic indicator and enforced Met expression in normal osteoblasts leads to genomic instability and malignant transformation. Met is also known to be inappropriately expressed in canine OSA tumour samples and cell lines. The purpose of this study was to evaluate the potential utility of an orally bioavailable small molecule Met inhibitor, PF2362376, against canine OSA cell lines as a prelude to future clinical work. PF2362376 inhibited phosphorylation of Met, Gab-1, Erk and Akt, but not of Src or STAT3. Furthermore, PF2362376 inhibited proliferation of canine OSA cell lines and induced cell death at biologically achievable concentrations. Last, activities associated with Met signalling including migration, invasion, branching morphogenesis and colony formation in soft agar were blocked by PF2362376. These studies support the notion that Met is a relevant target for therapeutic intervention in OSA.
Insights
A novel Met inhibitor, PF2362376, effectively targets canine osteosarcoma (OSA) by blocking Met signaling pathways. This research supports Met as a therapeutic target for canine OSA, paving the way for clinical applications.
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- The receptor tyrosine kinase Met is frequently dysregulated in human cancers, including osteosarcoma (OSA).
- Met overexpression in osteosarcoma correlates with poor prognosis and can induce malignant transformation.
- Aberrant Met expression is also observed in canine OSA tumors and cell lines.
Purpose of the Study:
- To investigate the efficacy of PF2362376, an oral small molecule Met inhibitor, against canine OSA cell lines.
- To assess the potential of PF2362376 as a therapeutic agent for canine osteosarcoma.
- To provide a preclinical basis for future clinical studies in canine OSA.
Main Methods:
- Utilized canine OSA cell lines for in vitro evaluation of PF2362376.
- Assessed the impact of PF2362376 on Met phosphorylation and downstream signaling pathways (Gab-1, Erk, Akt).
- Evaluated the effects of PF2362376 on cell proliferation, cell death, migration, invasion, and colony formation.
Main Results:
- PF2362376 effectively inhibited Met phosphorylation and downstream signaling, including Gab-1, Erk, and Akt.
- The inhibitor demonstrated significant suppression of canine OSA cell proliferation and induced cell death at achievable concentrations.
- PF2362376 blocked Met-associated activities such as migration, invasion, branching morphogenesis, and soft agar colony formation.
Conclusions:
- Met signaling is a relevant therapeutic target in canine osteosarcoma.
- PF2362376 shows significant preclinical efficacy against canine OSA cell lines.
- These findings support the further clinical investigation of PF2362376 for treating canine osteosarcoma.
