Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions
Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions
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DOI：
10.1053/j.gastro.2008.01.081
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发表时间：
2008-05-01
期刊：
影响因子：
29.4
通讯作者：
Ito, Akihk
中科院分区：
文献类型：
--
作者：
Koma, Yu-Ichiro;Furuno, Tadahide;Ito, Akihk
背景与目的：细胞粘附分子1（CADM 1）通过嗜同性结合介导神经-肥大细胞的粘附和通讯。免疫组织化学筛选显示CADM 1在胰岛中表达。在这里，我们确定了表达CADM 1的细胞类型，并研究了其在神经-胰岛细胞相互作用中的作用。方法：对小鼠和人胰腺及胰岛细胞瘤（ICT）进行免疫组化和免疫荧光双染色。在上级颈神经节的神经突网络上培养α TC 6细胞，一种鼠α细胞系。在蝎毒特异性激活神经后，检查神经突-α TC 6细胞的附着和通讯。结果如下：CADM 1在人类所有4种主要类型的胰岛细胞（α、β、D和胰多肽）的质膜上表达，但在小鼠中主要在α细胞中表达。在共培养中，α TC 6细胞与神经突的附着被抗CADM 1功能阻断抗体剂量依赖性地抑制。在对蝎毒诱发的神经激活的反应中，36%的α TC 6细胞动员了Ca 2+，并且引入CADM 1靶向小干扰RNA将反应细胞的比例降低到7%。在21例人ICT中，CADM 1存在于7例的质膜中，其余均为阴性。6个CADM 1表达肿瘤是功能性的，而除了2个CADM 1阴性肿瘤外，所有肿瘤都是无功能的（P = 0.0032）。结论：CADM 1是一种新的胰岛细胞粘附分子，介导神经-胰岛细胞相互作用。CADM 1表达与生殖功能表型之间的强相关性表明，CADM 1参与ICT的激素分泌。
Background & Aims: Cell adhesion molecule 1 (CADM1), mediates nerve-mast cell attachment and communication through homophilic binding. An immunohistochemical screen showed that CADM1 is expressed in pancreatic islets. Here, we determined the cell types expressing CADM1 and examined its role in nerve-islet cell interactions. Methods: Immunohistochemistry and double-staining immunofluorescence were performed on murine and human pancreases and on islet cell tumors (ICTs). alpha TC6 cells, a murine a cell line, were cultured on neurite networks of superior cervical ganglia. Neurite-alpha TC6 cell attachment and communication were examined after nerves were activated specifically by scorpion venom. Results: CADM1 was expressed on the plasma membrane in all 4 major types of islet cells, alpha, beta, D, and pancreatic polypeptide in human beings, but primarily in a cells in mice. In cocultures, alpha TC6 cell to neurite attachment was inhibited dose-dependently by an anti-CADM1 function-blocking antibody. In response to scorpion venom-evoked nerve activation, 36% of the alpha TC6 cells mobilized Ca2+, and introduction of a CADM1-targeting small interfering RNA reduced the fraction of responding cells to 7%. In 21 human ICTs, CADM1 was present in the plasma membrane of 7, and the others were negative for CADM1. Six of the CADM1-expressing tumors were functional hormonally, whereas all but 2 of the CADM1-negative tumors were nonfunctional (P = .0032). Conclusions: CADM1 is a novel islet cell adhesion molecule mediating nerve-islet cell interactions. The strong correlation between CADM1 expression and hormonally functional phenotypes suggests that CADM1 is involved in hormone secretion from ICTs.