Journal Article

Blocked expression of key genes of the angiogenic pathway in JSRV-induced pulmonary adenocarcinomas

Gineys, Barbara, Bobet Erny, Alexandra, Archer, Fabienne, Girard, Nicolas, Infections Virales et Pathologie Comparée - UMR 754 (IVPC) ; Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE) ; Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon, Plan Cancer; Ligue contre le Cancer, Ardeche, Mornex, Jean-François, Leroux, Caroline, Dolmazon, Christine, Gomes, Maryline

2017

Overview

AbstractJSRV (Jaagsiekte Sheep Retrovirus) is a retrovirus inducing a transmissible lung adenocarcinoma in sheep and goats with predominantly lepidic and papillary lesions. This naturally occurring lung cancer in large animals shares many features with human pneumonic-type lung adenocarcinomas with predominant lepidic growth. The metastatic spread is rare in both human and animal cancers. This unique feature prompted us to decipher the angiogenesis pathway in these cancers. We focused on the levels of mRNA and proteins of genes implicated in the extension of JSRV-induced lung adenocarcinomas by studying their expression in lung cancers (n = 10) and normal lungs (n = 10) and in primary epithelial alveolar type II cells derived from cancers (n = 10) or normal lungs (n = 6). In parallel, we evaluated the levels of expression of key genes in lung tissues collected from lepidic (n = 13) or papillary (n = 5) human adenocarcinomas and, when available, adjacent normal lungs (n = 11). We measured the expression of the same key genes implicated in angiogenesis, lymphangiogenesis and degradation of the extracellular matrix. In ovine adenocarcinomas, VEGFR2 and VEGFD mRNA were downregulated in cancers; MMP9, TIMP1 and FGFR2 mRNA were overexpressed as compared to normal lungs. Importantly, VEGFA and VEGFR2 proteins were not expressed in JSRV-induced cancers. In human lepidic adenocarcinomas, VEGFA and VEGFR2 mRNA were weakly expressed and no VEGFR2 protein was detectable. Downregulation of key angiogenic players may contribute to the control of extra thoracic invasion of cancer cells in human and ovine pneumonic-type adenocarcinoma with predominant lepidic growth.

• Publisher: HAL CCSD,BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma - metabolism / Adenocarcinoma of Lung / Adenocarcinoma, Papillary - genetics / Adenocarcinoma, Papillary - metabolism / Adult / Aged / Aged, 80 and over / Angiogenesis / Animals / Cancer / epithelium / Extracellular matrix / Female / fibroblast growth factor receptor 2 / Fibroblasts / Gene expression / Gene Expression Regulation, Neoplastic / Genes / Genetic aspects / Genomes / goats / Humans / Immunology / Jaagsiekte sheep retrovirus / Jaagsiekte sheep retrovirus - physiology / Life Sciences / Ligands / Lung - physiopathology / Lung cancer / lung neoplasms / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / lungs / Male / Medical prognosis / Medicine / Medicine & Public Health / messenger RNA / Metastasis / Microbiology / Middle Aged / neoplasm cells / Neovascularization, Pathologic - genetics / Neovascularization, Pathologic - veterinary / Protein expression / Proteins / Pulmonary Adenomatosis, Ovine - genetics / Pulmonary Adenomatosis, Ovine - metabolism / Research Article / RNA / Rodents / Sheep / Signal transduction / Trends / Vascular endothelial growth factor / vascular endothelial growth factor receptor-2 / Veterinary Medicine/Veterinary Science / Virology
• ISBN: 0004152688000