Molecular cloning of a cell-surface glycoprotein that can potentially discriminate mesothelium from epithelium: its identification as vascular cell adhesion molecule 1

Abstract

It has long been a practical problem for surgical pathologists to distinguish mesothelium from epithelium in order to make a positive diagnosis of mesothelioma. In this study, we developed a new monoclonal antibody, designated MS-2761 (IgG1, k), against cultured non-neoplastic mesothelial cells. Immunohistochemistry and slot-blot analysis revealed that this monoclonal antibody reacted with 100% (12/12) of benign and malignant mesothelioma tissues and a mesothelioma cell line, but not with 99% (77/78) of epithelial tumour tissues and 97% (33/34) of epithelial tumour cell lines. A gene encoding the cell-surface antigen defined by this monoclonal antibody was isolated from a mesothelial cell cDNA library constructed with a mammalian cell expression vector through transfection of Cos-7 cells and immunoselection by panning. DNA sequencing and a database search revealed that the gene was identical to vascular cell adhesion molecule 1 (VCAM1, also referred to as INCAM110). The prominent VCAM1 transcript in mesothelium was 3.2 kb in size with seven Ig-like domains, in addition to a minor transcripts with six Ig-like domains. This monoclonal antibody potentially discriminates mesothelium from epithelium and may become a tool for differential diagnosis of mesothelioma.