title: Increased expression of insulin-like growth factor-1 receptor is correlated with worse survival in canine appendicular osteosarcoma.
abstract: Insulin-like growth factor 1 receptor (IGF-1R) is a cell membrane receptor widely expressed in tissues and involved in different cancers in humans. IGF-1R expression in human osteosarcoma has been associated with the development of tumour metastasis and with prognosis, and represents an attractive therapeutic target. The goal of this study was to investigate the expression of IGF-1R in canine osteosarcoma tissues and cell lines and assess its role and prognostic value. Samples from 34 dogs were examined by immunohistochemistry for IGF-1R expression. IGF-1R/AKT/MAPK signalling was evaluated by western blot and quantitative polymerase chain reaction in the cell lines. In addition, the in vitro inhibition of IGF-1R with pycropodophillin (PPP) was used to evaluate molecular and biological effects. Immunohistochemical data showed that IGF-1R was expressed in 71% of the analysed osteosarcoma samples and that dogs with higher levels of IGF-IR expression (47% of cases) had decreased survival (P < 0.05) when compared to dogs with lower IGF-IR expression. Molecular studies demonstrated that in canine osteosarcoma IGF-IR is activated by IGF-1 mostly in a paracrine or endocrine (rather than autocrine) manner, leading to activation of AKT/MAPK signalling. PPP caused p-IGF-1R dephosphorylation with partial blocking of p-MAPK and p-AKT, as well as apoptosis. It was concluded that IGF-1R is expressed and plays a role in canine osteosarcoma and that its expression is correlated with a poor prognosis. As in humans, IGF-1R may represent a good therapeutic target and a prognostic factor for canine osteosarcoma.
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy. Electronic address: lorella.maniscalco@unito.it.
authors.forename: Lorella
authors.initials: L
authors.lastname: Maniscalco
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Selina
authors.initials: S
authors.lastname: Iussich
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morello
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Martano
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gattino
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Miretti
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Bartolomeo
authors.initials: B
authors.lastname: Biolatti
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Accornero
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Martignani
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Céspedes
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Buracco
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Braccini 2, Grugliasco, TO, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: De Maria
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000401:mortality / Q000662:veterinary*; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000378:metabolism* / Q000401:mortality; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism / Q000401:mortality / Q000662:veterinary*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D017526:Receptor, IGF Type 1
keywords: Comparative oncology; Dog; Insulin-like growth factor 1 receptor (IGF-1R); Osteosarcoma; Targeted therapy; Therapeutic target