title: Expression of cellular adhesion molecule 'OPCML' is down-regulated in gliomas and other brain tumours.
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 alpha1 and alpha2, 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 alpha2 variant. Hypermethylation of the alpha1 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.
authors.affiliation: JK Douglas Laboratories, Clatterbridge Hospital, Wirral, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Reed
authors.forename: J R
authors.initials: JR
authors.lastname: Dunn
authors.forename: D G
authors.initials: DG
authors.lastname: du Plessis
authors.forename: E J
authors.initials: EJ
authors.lastname: Shaw
authors.forename: P
authors.initials: P
authors.lastname: Reeves
authors.forename: A L
authors.initials: AL
authors.lastname: Gee
authors.forename: P C
authors.initials: PC
authors.lastname: Warnke
authors.forename: G C
authors.initials: GC
authors.lastname: Sellar
authors.forename: D J
authors.initials: DJ
authors.lastname: Moss
authors.forename: C
authors.initials: C
authors.lastname: Walker
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D005091:Exons / Q000235:genetics; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; C059785:OPCML protein, human; D012334:RNA, Neoplasm