文章：

化生：组织损伤适应和发育不良-癌症序列的前兆

Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence

原文发布日期：2017-09-01

DOI: 10.1038/nrc.2017.68

类型: Review Article

开放获取: 否

要点：

1. Metaplasia is the replacement of one differentiated cell type with another mature differentiated cell type that is not normally present in that tissue.
2. Metaplasia, when persistent, can be a precursor to dysplasia, which can in turn progress to carcinoma. As a result, recognition of metaplasia through screening and surveillance modalities is important and could reveal potential strategies for both cancer prevention and therapy.
3. Metaplasia is an adaptive response to injurious agents, which are largely environmental in nature (for example, acid, bile, cigarette smoke and alcohol), but is also influenced by the actions of microorganisms (for example, Helicobacter pylori and human papillomavirus (HPV)).
4. Different types of metaplasia exist, depending upon the tissue source: squamous, intestinal and acinar–ductal.
5. The cell of origin has been postulated to be from the gastric cardia in oesophageal intestinal metaplasia and to be triggered by loss of parietal cells in gastric intestinal metaplasia.
6. Metaplastic cell-autonomous (for example, mutant KRAS signalling) and non-cell-autonomous mechanisms contribute to the development and maintenance of metaplasia.

要点翻译：

1. 化生是指一种分化成熟的上皮细胞类型被另一种正常情况下并不存在于该组织的分化成熟的上皮细胞类型所取代。
2. 持续存在的化生可能是异型增生的前兆，而后者又可进展为癌。因此，通过筛查和监测手段识别化生至关重要，并可能为癌症的预防和治疗揭示潜在策略。
3. 化生是对损伤因子的适应性反应，这些因子主要源于环境（例如酸、胆汁、香烟烟雾和酒精），但也受微生物作用的影响（例如幽门螺杆菌和人乳头瘤病毒）。
4. 根据组织来源的不同，存在不同类型的化生：鳞状化生、肠化生和腺泡-导管化生。
5. 在食管肠化生中，起源细胞被推测来源于胃贲门部；而在胃肠化生中，则被认为由壁细胞缺失触发。
6. 化生细胞自主性（例如突变KRAS信号传导）和非细胞自主性机制共同促进了化生的发生和维持。

英文摘要：

Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar–ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.

摘要翻译： 

近几十年来，得益于治疗进展，大多数骨髓瘤患者的预后已有所改善。然而，仍有一部分被视为高危疾病的患者未能获益。若欲改善其预后，关键在于理解这种高危疾病是如何从治疗反应较好的阶段演变而来。这可以通过识别驱动正常浆细胞向以下疾病阶段演变的遗传机制和突变来实现：意义未明的单克隆丙种球蛋白病、冒烟型骨髓瘤、骨髓瘤以及浆细胞白血病。尽管骨髓瘤的起始事件是克隆性的，后续的驱动性病变往往发生在细胞的亚克隆中，并通过达尔文选择过程促进疾病进展。理解克隆与其微环境之间的共同演化，对于在治疗上干预这一过程至关重要。疾病进展的终末阶段表现为一种与治疗耐药、增殖增强、逃避凋亡以及能够在不依赖骨髓微环境的情况下独立生长的状态。在本综述中，我们探讨了这些终末期高危疾病状态，以及新信息如何增进我们对其演化轨迹的理解、如何诊断这些状态，并指出若要有效治疗，必须应对其生物学行为。

原文链接：

Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence