文章：

结肠隐窝组织与肿瘤发生

Colonic crypt organization and tumorigenesis

原文发布日期：2008-05-15

DOI: 10.1038/nrc2392

类型: Review Article

开放获取: 否

要点：

1. Intestinal crypts house the tissue-specific, multipotential stem cells located in the niche at the base of the crypt, capable of regenerating all intestinal cell types.
2. Intestinal crypts are clonal populations.
3. A stem cell that has acquired a mutation can expand to occupy the whole stem-cell niche, through genetic drift or by acquiring a selective advantage (niche succession); eventually their progeny can fill the whole crypt (monoclonal conversion).
4. Mutated intestinal crypts expand by crypt fission, leading to spread of the mutation within the epithelium (field cancerization).
5. Further genetic changes result in the appearance of the earliest recognizable lesion in the colon (the monocryptal adenoma); expansion by crypt fission results in the development of the premalignant lesion in the colon (the adenoma).
6. Adenomas appear to be polyclonal; short-range interactions between adjacent initiated clones might be responsible, with clonal interaction required for adenoma formation.
7. Although it is clear that many tumours arise from stem cells, there is early evidence that committed progenitor cells linger long enough in the crypt to undergo mutation and selection events that lead to neoplasia.
8. These concepts can be applied to other tissues and organs as a basis for the development of the earliest neoplastic lesions.

要点翻译：

1. 肠隐窝容纳着位于隐窝基底微环境中的组织特异性多能干细胞，这些干细胞能够再生所有肠道细胞类型。
2. 肠隐窝属于克隆群体。
3. 获得突变的干细胞可通过遗传漂变或获得选择性优势（微环境演替）扩展至整个干细胞微环境；最终它们的后代可充满整个隐窝（单克隆转化）。
4. 突变肠隐窝通过隐窝分裂进行扩张，导致突变在上皮细胞内扩散（场癌变效应）。
5. 进一步遗传改变导致结肠中出现最早可识别的病变（单隐窝腺瘤）；通过隐窝分裂的扩张形成结肠癌前病变（腺瘤）。
6. 腺瘤呈多克隆性；相邻起始克隆间的短程相互作用可能是成因，腺瘤形成需要克隆间相互作用。
7. 虽然许多肿瘤显然起源于干细胞，但早期证据表明定向祖细胞在隐窝中停留时间足够长，可经历导致肿瘤形成的突变和选择事件。
8. 这些概念可应用于其他组织和器官，作为最早期肿瘤性病变发生的基础。

英文摘要：

An appreciation of colonic crypt organization has become essential to any understanding of tumorigenesis in the colon. Intestinal crypts house tissue-specific, multipotential stem cells, which are located in the niche at the base of the intestinal crypt and are capable of regenerating all intestinal cell types. Recent advances in our understanding of crypt biology, including how mutations in stem cells become fixed and expand within the epithelium, has led to new theories on the origins of colonic adenomas and cancers.

摘要翻译： 

对结肠隐窝结构的理解已成为认识结肠癌发生的关键。肠隐窝内含有组织特异性的多能干细胞，这些干细胞位于隐窝基部的微环境中，能够再生所有类型的肠上皮细胞。近年来，对隐窝生物学认识的进展，包括干细胞突变如何在上皮中固定并扩增，为结直肠腺瘤和癌症的起源提供了新的理论。

原文链接：

Colonic crypt organization and tumorigenesis