文章：

朋友还是敌人——肿瘤基质在癌症中的双极效应

Friends or foes — bipolar effects of the tumour stroma in cancer

原文发布日期：2004-11-01

DOI: 10.1038/nrc1477

类型: Review Article

开放获取: 否

要点：

1. Cancer cells can alter their adjacent stroma to form a permissive and supportive environment for tumour progression — this is known as the 'reactive' tumour stroma.
2. Cancer cells produce a range of growth factors and proteases that modify their stromal environment.
3. These factors disrupt normal tissue homeostasis and act in a paracrine manner to induce angiogenesis and inflammation, as well as activation of surrounding stromal cell types such as fibroblasts, smooth-muscle cells and adipocytes, leading to the secretion of additional growth factors and proteases.
4. Activated fibroblasts in the stroma promote tumour progression by secreting growth factors and pro-migratory extracellular-matrix (ECM) components, as well as upregulating the expression of serine proteases and matrix metalloproteinases that degrade and remodel the ECM.
5. The induction of inflammation in the tumour stroma also results in production of a range of factors that promote tumour progression.
6. Angiogenesis promotes not only tumour growth, but also progression from a pre-malignant to a malignant and invasive tumour phenotype.
7. The tumour stroma can have a more direct role in tumorigenesis, by acting as a mutagen.
8. By 'normalizing' the tumour stroma, it is possible to slow or reverse tumour progression.

要点翻译：

1. 癌细胞能够改变其邻近的间质，形成允许并支持肿瘤进展的环境——这被称为“反应性”肿瘤间质。
2. 癌细胞产生一系列生长因子和蛋白酶，用以修饰其周围的间质环境。
3. 这些因子破坏正常组织稳态，并以旁分泌方式诱导血管生成和炎症反应，同时激活周围的基质细胞类型（如成纤维细胞、平滑肌细胞和脂肪细胞），导致额外的生长因子和蛋白酶分泌。
4. 间质中活化的成纤维细胞通过分泌生长因子、促迁移的细胞外基质成分，以及上调能够降解和重塑细胞外基质的丝氨酸蛋白酶和基质金属蛋白酶的表达，从而促进肿瘤进展。
5. 肿瘤间质中炎症反应的诱导也会产生一系列促进肿瘤进展的因子。
6. 血管生成不仅促进肿瘤生长，还推动肿瘤从前恶性状态向恶性及侵袭性表型发展。
7. 肿瘤间质还可作为诱变剂，在肿瘤发生中发挥更直接的作用。
8. 通过“正常化”肿瘤间质，有可能延缓或逆转肿瘤进展。

英文摘要：

The restricted view of tumour progression as a multistep process defined by the accumulation of mutations in cancer cells has largely ignored the substantial contribution of the tumour microenvironment to malignancy. Even though the seed and soil hypothesis of Paget dates to 1889, it has been less than two decades since researchers have included the tumour microenvironment in their analyses of tumour progression. What have we recently learned from studying tumour–stroma interactions, and will this help to define new targets for therapy?

摘要翻译： 

将肿瘤进展视为由癌细胞突变累积所定义的多步骤过程的狭隘观点，在很大程度上忽略了肿瘤微环境对恶性的重要贡献。尽管Paget的“种子与土壤”假说可追溯至1889年，但研究人员将肿瘤微环境纳入肿瘤进展分析的时间尚不足二十年。我们最近从肿瘤-基质相互作用的研究中学到了什么？这将有助于确定新的治疗靶点吗？

原文链接：

Friends or foes — bipolar effects of the tumour stroma in cancer