دورية أكاديمية
أعرض في EDS

The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.

التفاصيل البيبلوغرافية
العنوان: The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.
المؤلفون: Harris ED; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada., Sharpe JC; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada., Strozen T; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada., Abdi S; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada., Kliewer M; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada., Sanchez MG; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada.; Department of Biochemistry, Microbiology and Immunology, College of Medicine, University of Saskatchewan, GA20 Health Sciences, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada., Hogan NS; Department of Animal and Poultry Science, College of Agriculture and Bioresources, University of Saskatchewan, 51 Campus Drive, Saskatoon, SK S7N 5A8, Canada., MacDonald-Dickinson V; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada., Vizeacoumar FJ; Cancer Research, Saskatchewan Cancer Agency and Division of Oncology, University of Saskatchewan, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada., Toosi BM; Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada.
المصدر: Cells [Cells] 2024 Jul 16; Vol. 13 (14). Date of Electronic Publication: 2024 Jul 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Cell Movement*/drug effects , Cell Movement*/genetics , Neoplasm Invasiveness* , Osteosarcoma*/pathology , Osteosarcoma*/metabolism , Osteosarcoma*/drug therapy , Osteosarcoma*/genetics , Receptor, EphA2*/metabolism , Receptor, EphA2*/genetics, Animals ; Dogs ; Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/metabolism ; Bone Neoplasms/pathology ; Bone Neoplasms/drug therapy ; Bone Neoplasms/genetics ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Cisplatin/therapeutic use ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic/drug effects
مستخلص: 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.
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معلومات مُعتمدة: 4990 Saskatchewan Health Research Foundation; NA Companion Animal Health Fund (CAHF); NA Allard Research Chair in Oncology Start-up Fund
فهرسة مساهمة: Keywords: EphA2; cancer invasion; comparative oncology; osteosarcoma
المشرفين على المادة: 0 (Antineoplastic Agents)
Q20Q21Q62J (Cisplatin)
EC 2.7.10.1 (Receptor, EphA2)
0 (EPHA2 protein, human)
تواريخ الأحداث: Date Created: 20240726 Date Completed: 20240726 Latest Revision: 20240731
رمز التحديث: 20240801
مُعرف محوري في PubMed: PMC11275032
DOI: 10.3390/cells13141201
PMID: 39056783
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells13141201