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IL-4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells.
Bauer, K; Hadzijusufovic, E; Cerny-Reiterer, S; Hoermann, G; Reifinger, M; Pirker, A; Valent, P; Willmann, M.
Afiliación
  • Bauer K; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
  • Hadzijusufovic E; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
  • Cerny-Reiterer S; Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
  • Hoermann G; Department/Clinic for Companion Animals and Horses, Clinic for Small Animals, Clinical Unit of Internal Medicine, University of Veterinary Medicine Vienna, Vienna, Austria.
  • Reifinger M; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
  • Pirker A; Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
  • Valent P; Department for Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
  • Willmann M; Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
Vet Comp Oncol ; 15(4): 1240-1256, 2017 Dec.
Article en En | MEDLINE | ID: mdl-27507155
CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this 'comparative oncology' study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mastocitosis / Interleucina-4 / Antígeno Ki-1 / Enfermedades de los Perros Límite: Animals Idioma: En Revista: Vet Comp Oncol Asunto de la revista: MEDICINA VETERINARIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mastocitosis / Interleucina-4 / Antígeno Ki-1 / Enfermedades de los Perros Límite: Animals Idioma: En Revista: Vet Comp Oncol Asunto de la revista: MEDICINA VETERINARIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido