Expression of cellular adhesion molecule 'OPCML' is down-regulated in gliomas and other brain tumours

Reed, J. E. and Dunn, Julie R. and du Plessis, Daniel and Shaw, Elisabeth and Reeves, P. and Gee, A. and Warnke, Peter C. and Sellar, G. C. and Moss, D. J. and Walker, C. (2007) Expression of cellular adhesion molecule 'OPCML' is down-regulated in gliomas and other brain tumours. Neuropathology and Applied Neurobiology, 33 (1). pp. 77-85. ISSN 0305-1846

Abstract

The four GPI-anchored cell adhesion molecules that exemplify the IgLON family are most highly expressed in the nervous system and associate to form up to six different heterodimeric ‘Diglons’ that can modify cell adhesion and inhibit axon migration. Recently, two members, OPCML and LSAMP, were identified as putative tumour suppressor genes in ovarian and renal carcinomas respectively. In this study, we investigated OPCML expression in nonneoplastic brain tissue and 35 brain tumours (18 glioblastoma multiformes, five anaplastic gliomas, five meningiomas, six metastases and one medulloblastoma) and four glioma cell lines using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). OPCML was highly expressed in cerebellum, less so in cerebral cortex, frontal lobe and meninges and was significantly reduced or absent in 83% of brain tumours and all cell lines compared with nonneoplastic whole brain. Two OPCML splice variants have been identified in humans, termed α1 and α2, but the latter has not been demonstrated in human neural tissues. Using PCR with specific primers, nonneoplastic brain and 3/6 of tested brain tumours expressed both splice variants, whereas the remaining brain tumours only expressed the α2 variant. Hypermethylation of the α1 OPCML promoter, associated with down-regulation of expression in ovarian tumours, did not correlate with expression levels in the subset of brain tumours tested, implying transcription of OPCML from an alternative promoter or a different mechanism of down-regulation. This study demonstrates that OPCML down-regulation occurs in the majority of brain tumours tested, warranting further investigation of OPCML and other IgLONs in the development and progression of brain tumours.