Reed J E, Dunn J R, du Plessis D G, Shaw E J, Reeves P, Gee A L, Warnke P C, Sellar G C, Moss D J, Walker C
JK Douglas Laboratories, Clatterbridge Hospital, Wirral, UK.
Neuropathol Appl Neurobiol. 2007 Feb;33(1):77-85. doi: 10.1111/j.1365-2990.2006.00786.x.
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.
代表IgLON家族的四种糖基磷脂酰肌醇（GPI）锚定细胞粘附分子在神经系统中表达最高，并结合形成多达六种不同的异二聚体“双IgLON”，它们可改变细胞粘附并抑制轴突迁移。最近，两个成员，即OPCML和LSAMP，分别被鉴定为卵巢癌和肾癌中的潜在肿瘤抑制基因。在本研究中，我们使用定量逆转录聚合酶链反应（RT-PCR）研究了OPCML在非肿瘤性脑组织和35例脑肿瘤（18例多形性胶质母细胞瘤、5例间变性胶质瘤、5例脑膜瘤、6例转移瘤和1例髓母细胞瘤）以及4种胶质瘤细胞系中的表达情况。OPCML在小脑中高度表达，在大脑皮层、额叶和脑膜中表达较少，与非肿瘤性全脑相比，83%的脑肿瘤和所有细胞系中OPCML表达显著降低或缺失。在人类中已鉴定出两种OPCML剪接变体，称为α1和α2，但后者尚未在人类神经组织中得到证实。使用特异性引物进行PCR，非肿瘤性脑和6例受试脑肿瘤中的3例表达了两种剪接变体，而其余脑肿瘤仅表达α2变体。α1 OPCML启动子的高甲基化与卵巢肿瘤中表达下调有关，但与受试脑肿瘤亚组中的表达水平无关，这意味着OPCML是从另一个启动子转录而来，或者存在不同的下调机制。本研究表明，在大多数受试脑肿瘤中发生了OPCML下调，这值得进一步研究OPCML和其他IgLONs在脑肿瘤发生和发展中的作用。
