Disease relevance of OPCML

• These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG [1].
• Expression of cellular adhesion molecule 'OPCML' is down-regulated in gliomas and other brain tumours [2].
• Recently, two members, OPCML and LSAMP, were identified as putative tumour suppressor genes in ovarian and renal carcinomas respectively [2].
• 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) [2].
• In this paper we report the effect of recombinant LAMP, CEPU-1 and OBCAM, and transfected cell lines expressing these molecules, on the adhesion and outgrowth of dorsal root ganglion (DRG) and sympathetic neurones [3].

High impact information on OPCML

• Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain-containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC [1].
• The sequence homologies of the purified opioid-binding protein OBCAM with tyrosine kinase growth factor receptors suggest additional possibilities for second messengers [4].
• An antibody raised to a portion of the predicted amino acid sequence of opioid-binding cell-adhesion molecule (OBCAM) specifically labeled the surface of NG108-15 cells, as visualized by immunofluorescence with confocal microscopy [5].
• Previous work has shown that limbic-system-associated protein (LAMP), CEPU-1/Neurotrimin and OBCAM interact homophilically and heterophilically within the family [6].
• Furthermore, although singly transfected cell lines have little effect on neurite outgrowth, CHO cell lines expressing both CEPU-1 and OBCAM (Diglon-CO) inhibit neurite outgrowth from cerebellar granule cells [6].

Biological context of OPCML

• Opioid binding protein/cell adhesion molecule-like gene (OPCML), a recently identified tumor-suppressor, is frequently inactivated by allele loss and CpG island promoter methylation in epithelial ovarian cancer [7].
• Furthermore, suppression of oncogenic RAS activity by stable siRNA specific for HRAS(V12) led to the demethylation and re-expression of OPCML in T29H cells, demonstrating that oncogenic RAS activity is directly responsible for the observed OPCML promoter hypermethylation and epigenetic gene silencing of OPCML [7].
• 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 [2].
• Opioid-binding protein/cell adhesion molecule-like (OPCML) gene and promoter methylation status in women with ovarian cancer [8].
• Methylation status of OPCML promoter region was studied with methylation-specific PCR (MSP) method [8].

Anatomical context of OPCML

• RAS-mediated epigenetic inactivation of OPCML in oncogenic transformation of human ovarian surface epithelial cells [7].
• 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 [2].
• OBCAM was mapped to human chromosome 11 by hybridizing the probe with a somatic cell hybrid panel [9].
• When anti-OBCAM peptide antibodies were used for immunoblots of CHO cells, untransfected, non-binding transfected, and high binding transfected cells revealed the same banding patterns with approximately equal intensity [10].

Associations of OPCML with chemical compounds

• cDNA cloning of the CEPUS, a secreted type of neural glycoprotein belonging to the immunoglobulin-like opioid binding cell adhesion molecule (OBCAM) subfamily [11].

Other interactions of OPCML

• Two OPCML splice variants have been identified in humans, termed alpha1 and alpha2, but the latter has not been demonstrated in human neural tissues [2].
• When delta-opioid receptor cDNA (DOR-1) was expressed in CHO cells, OBCAM immunoreactivity (OBCAM-ir) was detected [10].

Analytical, diagnostic and therapeutic context of OPCML

• Methylation-sensitive PCR analysis showed that the OPCML promoter was hypermethylated in RAS-transformed human ovarian epithelial cells (T29H) and that treatment with the DNA methyltransferase inhibitor 5'-aza-2'-deoxycytidine promoted demethylation of the OPCML promoter and restored OPCML expression in T29H cells [7].
• Sequence analysis of the ORF revealed 93% identity to the rat OBCAM cDNA at the nucleotide level, and the deduced amino-acid sequences shared 98% identity [9].
• The positive control, neural cell adhesion molecule (NCAM), a protein with structural homology to OBCAM, displayed the same levels of immunofluorescence in transfected and nontransfected cell lines [10].

References