Enteric Glia: The Origin of Duodenal Gastrinomas?
Enteric Glia: The Origin of Duodenal Gastrinomas?
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肠胶质细胞：十二指肠胃泌素瘤的起源？
DOI：
10.1053/j.gastro.2017.10.029
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发表时间：
2017
期刊：
影响因子：
29.4
通讯作者：
Gulbransen,BrianD
中科院分区：
文献类型：
--
作者：
Gulbransen,BrianD
多发性内分泌瘤1(MEN1)是一种罕见的常染色体显性遗传病，以内分泌腺和十二指肠肿瘤的发展为特征。十二指肠胃泌素瘤(胃泌素分泌神经内分泌肿瘤)经常与MEN1突变有关，但其自然病史知之甚少。这限制了针对这些人的严重并发症，如高胃泌素血症引起的溃疡和严重腹泻的新疗法的开发。Sundaresan等人在本期《胃肠病学》上的新发现有可能克服这一障碍，为MEN1相关十二指肠胃泌素瘤的产生机制提供重要的新见解。令人惊讶的是，这些发现表明，与MEN1相关的十二指肠胃泌素瘤来自一种意想不到的来源，即肠道胶质。胃泌素瘤最初由Zollinger和Ellison 2描述为胰腺神经内分泌肿瘤，2但此后变得明显的是，大多数胃泌素瘤位于十二指肠。3十二指肠和胰腺胃泌素瘤现在被认为在发育和功能上是不同的，也许除了产生胃泌素的能力之外，它们没有更多的共同之处。4同样，十二指肠胃泌素瘤的亚型本身在发育和生物学功能上也是不同的。例如，散发性胃泌素瘤是典型的孤立性肿瘤，而MEN1胃泌素瘤通常是多中心的，与MEN1相关，但不是散发性的，十二指肠胃泌素瘤与肿瘤发生之前的增殖胃泌素细胞变化有关。6.
Multiple endocrine neoplasia 1 (MEN1) is a rare autosomal-dominant disorder characterized by the development of tumors in endocrine glands and the duodenum. Duodenal gastrinomas (gastrin-secreting neuroendocrine tumors) are frequently associated with MEN1 mutations, but their natural history is poorly understood. This limits the development of new therapies for serious complications such as ulcers and severe diarrhea caused by hypergastrinemia in these individuals. New findings in this issue of Gastroenterology by Sundaresan et al 1 have the potential to overcome this roadblock by providing important new insight into the mechanisms that produce MEN1-associated duodenal gastrinomas. Surprisingly, these findings suggest that MEN1-associated duodenal gastrinomas arise from an unexpected source, enteric glia.Gastrinomas were originally described as pancreatic neuroendocrine tumors by Zollinger and Ellison, 2 but since then it has become clear that most gastrinomas are located in the duodenum. 3 Duodenal and pancreatic gastrinomas are now recognized as being developmentally and functionally distinct and perhaps share noting more in common than their ability to produce gastrin. 4 Likewise, subtypes of duodenal gastrinomas, themselves, are distinct in their development and biological functions. For example, sporadic gastrinomas are typically solitary tumors whereas MEN1 gastrinomas are usually multicentric, 5 and MEN1-associated, but not sporadic, duodenal gastrinomas are associated with proliferative gastrin cell changes that precede tumor development. 6