文章：

皮肤癌中的干细胞等级

Stem-cell hierarchy in skin cancer

原文发布日期：2003-06-01

DOI: 10.1038/nrc1095

类型: Review Article

开放获取: 否

要点：

1. Cancer is not a cell-autonomous disease, but involves disruption of the complex system of controls exerted by the local microenvironment, as well as hormonal or immune-system components produced by the whole organism.
2. Cancer, like any other tissue that is capable of regeneration or progressive growth, must have cells with self-renewal capacity and a hierarchical architecture.
3. Although many tumours contain cells with the characteristics of stem cells, the identity of the normal cells that acquire the first genetic hits leading to initiation of carcinogenesis has remained elusive. Although expression of stem-cell markers might reflect the tumour cell of origin, it remains possible that these markers are induced by the oncogenic events that occur after the initiation of neoplastic growth.
4. It is likely that there is a continuum of target cells for carcinogenesis, and that combinations of the particular cells in which mutations occur, as well as the specific genes altered, are the main determinants of cell fate and malignant potential.
5. Tumour promoters, which are not in themselves mutagenic, might affect the specific choice of initiated cell that forms a visible lesion and allows the selection of particular target cells.
6. Oncogenic events allow proliferation and self-renewal genetic programmes to be reconciled within the developing tumour.

要点翻译：

1. 癌症并非一种细胞自主性疾病，而是涉及局部微环境调控复杂系统以及整个机体产生的激素或免疫系统成分的破坏。
2. 与任何具有再生或进行性生长能力的组织一样，癌症必须拥有具备自我更新能力的细胞和层级结构。
3. 尽管许多肿瘤含有具有干细胞特征的细胞，但获得首个遗传打击导致癌变启动的正常细胞身份仍不明确。虽然干细胞标志物的表达可能反映肿瘤细胞的起源，但这些标志物仍有可能由肿瘤生长启动后发生的致癌事件所诱导。
4. 致癌作用的靶细胞很可能存在一个连续谱系，突变发生的特定细胞组合以及改变的具体基因，共同决定了细胞命运和恶性潜能的主要决定因素。
5. 本身不具有致突变性的肿瘤促进剂，可能会影响形成可见病变的启动细胞的特异性选择，并允许特定靶细胞的筛选。
6. 致癌事件使增殖和自我更新的遗传程序能够在发展中的肿瘤中实现协调。

英文摘要：

Tumour architecture mimics many of the features of normal tissues, with a cellular hierarchy that regulates the balance between cell renewal and cell death. Although many tumours contain cells with the characteristics of stem cells, the identity of the normal cells that acquire the first genetic hits leading to initiation of carcinogenesis has remained elusive. Identification of the primary cell of origin of cancers and the mechanisms that influence cell-fate decisions will be crucial for the development of novel non-toxic therapies that influence tumour-cell behaviour.

摘要翻译： 

肿瘤结构模拟了正常组织的许多特征，具有调控细胞更新与死亡平衡的细胞层级结构。尽管许多肿瘤含有具备干细胞特征的细胞，但那些获得最初遗传打击、启动癌变的正常细胞身份仍不清楚。明确癌症的起源细胞及影响细胞命运决定的机制，对于开发能够调控肿瘤细胞行为的新型无毒疗法至关重要。

原文链接：

Stem-cell hierarchy in skin cancer