Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours

Abstract

Human bronchioloalveolar carcinoma (BAC) is a lung cancer, morphologically similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary adenomatosis (SPA) or jaagsiekte. SPA is caused by an exogenous type B/D retrovirus (jaagsiekte sheep retrovirus (JSRV)), which prompted the present study to obtain evidence of a retrovirus in BAC.A panel of 249 human lung tumours, 21 nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other organs and a cell line expressing a human endogenous retrovirus protein was examined immunohistochemically using a rabbit antiserum directed against the JSRV capsid protein.Specific staining was detected only in the cytoplasm of recognizably neoplastic cells in the pulmonary alveoli of 39 of 129 (30%) BACs, 17 of 65 (26%) lung adenocarcinomas and two of seven large cell carcinomas. The remaining samples were negative.These results support the hypothesis that some human pulmonary tumours may be associated with a jaagsiekte sheep retrovirus-related retrovirus, warranting further studies. Eur Respir J 2000; 15: 330±332.

Evaluation of the 3p21.3 tumour-suppressor gene cluster

“…Although human HYAL2 can function as a receptor for JSRV it is not reported to cause lung cancer in humans exposed to the virus. However, antisera against the JSRV capsid protein reacts with a third of human pulmonary adenocarcinoma samples suggesting that a related virus may cause human disease (De las Heras et al, 2000). The ability of the JSRV Env to transform the bronchial epithelial cell line BEAS-2B depends on the activation of MST1R (a cell surface receptor tyrosine kinase also known as receptor tyrosine kinase (RON) that is located at 3p21.31).…”

Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep

“…Interestingly, de las Heras et al [17] showed the presence of an antigen crossreacting with JSRV-Gag antiserum in about 30% of human BAC, and 26% of lung adenocarcinomas. However, these results have not been confirmed by further molecular studies and 2 PCR-based analyses failed to detect any exogenous or endogenous JSRV-related genome in human BAC and adenocarcinoma [35,92].…”

Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus

“…In sheep JSRV causes a contagious form of lung cancer that arises from epithelial cells in the lower airway including type II alveolar and bronchiolar epithelial cells (5). In a recent study it was shown that antiserum directed against the JSRV capsid protein crossreacted with 30% of human pulmonary adenocarcinoma samples but not with normal lung tissue or adenocarcinomas from other tissues (6). Collectively these findings support the possibility (7) of a viral etiology for some human lung cancers, particularly the bronchioloalveolar adenocarcinoma (BAC) type, which is morphologically very similar to the sheep tumors (5,8).…”