title: Platelet-derived growth factors and receptors in Canine Lymphoma.
abstract: Platelet-derived growth factors (PDGFs) belong to a family of polypeptide growth factors that signal through cell surface tyrosine kinase receptors to stimulate growth, proliferation and differentiation. Platelet-derived growth factor receptors (PDGFRs) are also considered important targets for specific kinase inhibitors in the treatment of several human tumours. The aim of this study was to investigate the role of PDGF-A, PDGF-B, PDGFR-α and PDGFR-β in canine lymphoma by determining gene and protein expression in lymph nodes of dogs with diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), T-lymphoblastic lymphoma (T-LBL) and in healthy control dogs. One lymph node was also studied at the end of therapy in a subset of dogs in remission for DLBCL. In controls, PDGF-A, PDGFR-α and PDGFR-β mRNA levels were significantly higher than in DLBCLs, PTCLs and T-LBLs. However, PDGFR-α and PDGFR-β were minimally expressed by lymphocytes and plasma cells in normal lymph nodes as determined by immunohistochemistry, while neoplastic B and T cells showed the highest score (P <0.05). This discordant result may be compatible with the constitutive expression of these molecules by endothelial cells and fibroblasts in normal lymph nodes, thereby influencing gene expression results. Furthermore, these cells were not included in the immunohistochemical analysis. Similarly, dogs with DLBCL that were in remission at the end of therapy showed significantly higher gene expression of PDGFs and receptors than at the time of diagnosis and with an opposite trend to the protein assay. PDGF-B protein and mRNA were overexpressed in PTCLs and T-LBLs when compared with DLBCLs and controls (P <0.05). Additionally, there was a correlation between protein expression of PDGF-B and both PDGFRs in PTCLs and T-LBLs, suggesting an autocrine or paracrine loop in the aetiology of aggressive canine T-cell lymphomas. These data provide a rationale for the use of PDGFR antagonists in the therapy of aggressive T-cell lymphomas, but not in DLBCLs.
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis, Legnaro, PD, Italy. Electronic address: arianna.arico@unipd.it.
authors.forename: A
authors.initials: A
authors.lastname: Aricò
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis, Legnaro, PD, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Guadagnin
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis, Legnaro, PD, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ferraresso
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis, Legnaro, PD, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Gelain
authors.affiliation: Department of Veterinary Science, University of Torino, Via Leonardo da Vinci 44, 10095 Grugliasco, TO, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Iussich
authors.affiliation: Clinical Pathology, Department of Pathobiology, University of Veterinary Medicine of Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: B C
authors.initials: BC
authors.lastname: Rütgen
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis, Legnaro, PD, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mazzariol
authors.affiliation: Centro Oncologico Veterinario, via San Lorenzo 1-4, 40037 Sasso Marconi, BO, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Marconato
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis, Legnaro, PD, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Aresu
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D007150:Immunohistochemistry; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor
keywords: angiogenic factors; canine lymphoma; platelet-derived growth factor; therapy