title: Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells.
abstract: Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA. lawrence.uga@gmail.com
authors.forename: J
authors.initials: J
authors.lastname: Lawrence
authors.forename: C
authors.initials: C
authors.lastname: Saba
authors.forename: R
authors.initials: R
authors.lastname: Gogal
authors.forename: O
authors.initials: O
authors.lastname: Lamberth
authors.forename: M L
authors.initials: ML
authors.lastname: Vandenplas
authors.forename: D J
authors.initials: DJ
authors.lastname: Hurley
authors.forename: P
authors.initials: P
authors.lastname: Dubreuil
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.forename: K
authors.initials: K
authors.lastname: Dobbin
authors.forename: M
authors.initials: M
authors.lastname: Turek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002371:Cat Diseases / Q000188:drug therapy*; D002415:Cats; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D010880:Piperidines; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011725:Pyridines; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy / Q000662:veterinary*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D013844:Thiazoles / Q000627:therapeutic use; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010880:Piperidines; D010982:Platelet-Derived Growth Factor; D011725:Pyridines; D013844:Thiazoles; D015164:Vaccines, Inactivated; D017479:Receptors, Platelet-Derived Growth Factor; C526575:masitinib