RESUMO
Osteosarcoma is an aggressive bone cancer affecting both humans and dogs, often leading to pulmonary metastasis. Despite surgery and chemotherapy being the primary treatment modalities, survival rates remain low in both species, underscoring the urgent need for more efficacious therapeutic options. Accumulating evidence indicates numerous biological and clinical similarities between human and canine osteosarcoma, making it an ideal choice for comparative oncological research that should benefit both species. The EphA2 receptor has been implicated in controlling invasive responses across different human malignancies, and its expression is associated with poor prognosis. In this study, we utilized a comparative approach to match EphA2 functions in human and canine osteosarcoma models. Our objectives were to assess EphA2 levels and its pro-malignant action in osteosarcoma cells of both species. We found that EphA2 is overexpressed in most of both canine and human osteosarcoma cell lines, while its silencing significantly reduced cell viability, migration, and invasion. Moreover, EphA2 silencing enhanced the sensitivity of osteosarcoma cells to cisplatin, a drug commonly used for treating this cancer. Furthermore, inhibition of EphA2 expression led to a significant reduction in tumor development capability of canine osteosarcoma cells. Our data suggest that these EphA2 effects are likely mediated through various signaling mechanisms, including the SRC, AKT, and ERK-MAPK pathways. Collectively, our findings indicate that EphA2 promotes malignant behaviors in both human and canine osteosarcoma and that targeting EphA2, either alone or in combination with chemotherapy, could offer potential benefits to osteosarcoma patients.
Assuntos
Movimento Celular , Invasividade Neoplásica , Osteossarcoma , Receptor EphA2 , Animais , Cães , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Receptor EphA2/metabolismo , Receptor EphA2/genéticaRESUMO
A 16-month-old Sarplaninac Shepherd cross dog presented for a 1-month history of a productive cough that was unresponsive to an empirical 10-day course of cephalexin. Thoracic computed tomography (CT) showed multifocal, well-defined, smoothly marginated, soft tissue attenuating, minimally contrast enhancing nodular airway mural thickenings protruding into the airway lumen in the caudal trachea and principal bronchi. These nodules were also visualized on bronchoscopy, and cytology revealed parasitic larvae consistent with Oslerus osleri. The dog was treated with oral fenbendazole for 26 days. Clinical signs resolved within 3 weeks of treatment initiation and had not relapsed at 7-month follow-up.