文章：

将肿瘤置于背景中

Putting tumours in context

原文发布日期：2001-10-01

DOI: 10.1038/35094059

类型: Review Article

开放获取: 否

要点：

1. Cell–cell and cell–ECM signalling contributes to epithelial structure and function and creates innate anticancer mechanisms that suppress tumorigenicity.
2. The development of carcinomas involves progressive changes in the malignant cells, in the associated stromal compartment and in the extracellular milieu. These changes lead to an ever-changing functional disorder, in which the aberrant context affects cell–cell and tissue–tissue interactions.
3. The tumour context includes both normal cells and tissues that aid in the progression of the tumour. The tumour, in turn, modifies the behaviour of the 'normal' component of the tumour.
4. The tumour context is both self-sustaining and progressive, but can be modified through alterations in signalling that affect the structure and function of tumour cells; malignant epithelial cells can be reverted to a normal phenotype despite the aberrant genotype.
5. To achieve reversion of a tumour tissue, both the tumour cells and their microenvironment need to be modified. As such, a combination of signalling inhibitors and agents that 'deactivate' the reactive stroma is required.
6. Haematologic tumours develop (and can now be treated) according to many of these same principles.
7. A better understanding of the mechanisms by which the tumour context creates the functional disorder within the tumour organ is a means of potentiating existing anticancer therapies and of developing a new generation of even more successful therapies.

要点翻译：

1. 细胞间及细胞与细胞外基质（ECM）的信号传导共同维持上皮结构功能，并形成抑制肿瘤发生的天然抗癌机制。
2. 癌变过程涉及恶性细胞、相关基质区室及细胞外微环境的渐进性改变，这些变化导致功能紊乱持续动态演变——异常微环境通过干扰细胞间及组织间相互作用推动肿瘤发展。肿瘤微环境既包含促进肿瘤进展的正常细胞与组织，同时肿瘤又反向调控这些"正常"组分的行为。
3. 这种微环境具有自我维持和持续演进特性，但可通过改变信号传导来重塑肿瘤细胞的结构功能：即使存在异常基因型，恶性上皮细胞仍可逆转为正常表型。
4. 要实现肿瘤组织的表型逆转，必须同步改造肿瘤细胞及其微环境。因此需要联合使用信号传导抑制剂和"灭活"反应性基质的药物。
5. 血液系统肿瘤的发生发展（及现有治疗方法）同样遵循这些原理。
6. 深入理解肿瘤微环境如何导致肿瘤器官功能紊乱的机制，将有助于增强现有抗癌疗法的效力，并推动新一代更高效治疗策略的研发。

英文摘要：

The interactions between cancer cells and their micro- and macroenvironment create a context that promotes tumour growth and protects it from immune attack. The functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses. Investigation of this process might provide new insights into the mechanisms of tumorigenesis and could also lead to new therapeutic targets.

摘要翻译： 

癌细胞与其微环境及宏观环境之间的相互作用形成了一种促进肿瘤生长并保护其免受免疫攻击的背景。癌细胞与周围组织的功能关联形成了一个新的“器官”，这一器官会随着恶性肿瘤的进展而变化。对该过程的研究可能为肿瘤发生机制提供新的见解，并有望带来新的治疗靶点。

原文链接：

Putting tumours in context