RESUMEN
BACKGROUND: The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. METHODS: We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR. RESULTS: Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma). CONCLUSIONS: The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.
Asunto(s)
Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Hemangiosarcoma/metabolismo , Neovascularización Patológica , Animales , Línea Celular Tumoral , Perros , Femenino , Hemangiosarcoma/veterinaria , Humanos , Inflamación , Masculino , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteínas ras/genéticaRESUMEN
Hematopoietic malignancies are the most commonly reported neoplasms in lizards, occurring sporadically as in other reptiles. An unusually high incidence of lymphoid neoplasia occurred in a collection of Egyptian spiny-tailed lizards (Uromastyx aegyptius) from 1993-2001. Eight of 15 lizards necropsied at the Louisville Zoological Garden (53%) had multicentric lymphoma. Immunohistochemistry was not useful in characterizing the lineage of normal or neoplastic lymphocytes. By light and electron microscopy (EM), the neoplasms had plasmacytoid morphologic features suggesting B-cell origin, although some tumors also had a primitive lymphoblast component. A concurrent leukemic blood profile was identified in seven of the cases (88%). All were adult animals and no sex predilection was observed. No exposure to exogenous carcinogens was observed. Some of the lizards were unrelated, so hereditary factors were unlikely. Although examination by EM and viral isolation performed on archived tissues and plasma failed to detect viruses, an infectious etiology still warrants consideration.
Asunto(s)
Leucemia/veterinaria , Lagartos , Linfoma de Células B/veterinaria , Animales , Animales de Zoológico , Linfocitos B/citología , Linfocitos B/patología , Egipto/epidemiología , Femenino , Inmunohistoquímica/veterinaria , Incidencia , Leucemia/epidemiología , Leucemia/patología , Linfoma de Células B/epidemiología , Linfoma de Células B/patología , MasculinoRESUMEN
Pancreatic islet fibrosis with varying degrees of islet cell hyperplasia or islet effacement was diagnosed histologically in 19 rock hyraxes (Procavia capensis) from seven zoological parks. Some, but not all, affected hyraxes were from a common lineage. The condition was associated with apparent hyperglycemia in seven and diabetes mellitus in two. Immunohistochemistry revealed hyperplasia of beta, alpha, and delta cells proportional to the degree of the fibrosis. Electron microscopy revealed collagen deposition and fibroplasia within and around the islets. Special stains and electron microscopy were negative for the presence of amyloid. Beta cell depletion was never identified. The condition has morphologic features that resemble islet fibrosis of human infants born to diabetic mothers.