Clinical and Biological Implications of the Tumor Microenvironment
Clinical and Biological Implications of the Tumor Microenvironment
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DOI：
10.1007/s12307-012-0099-6
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发表时间：
2012-08-01
影响因子：
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通讯作者：
Tarin, David
中科院分区：
文献类型：
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作者：
Tarin, David
在正常组织和器官中，组成细胞的活动严格限于发育期间分配给它们的任务。此外，它们（白细胞除外）通过与邻近细胞的相互调节作用，仍然被严格限制在它们的领域内。这就创造了专门的局部微观环境，在这种环境中，结构和功能是有序的、稳定的，并在相互作用的调节网络内受到反馈回路的严格控制。这个系统有相当大的能力来适应不断变化的条件。相反，肿瘤形成和扩展区域的微环境的特征在于特化或分化的细胞功能的进行性丧失、无序的分子信号、显微器官结构的退化。这与细胞进出肿瘤的交通相结合，通常最终导致局部浸润和转移到其他器官。根据定义，这些被干扰的分子和细胞相互作用的性质是高度不稳定的，并且随着时间的推移越来越不可预测。它在不同的肿瘤之间也存在差异，有时甚至导致退化。然而，使用多种现代研究技术对肿瘤微观世界中的这种功能障碍进行的系统分析表明，所有活跃生长的原发性和继发性肿瘤都绝对依赖于宿主邻近非肿瘤细胞的支持。反过来，这种支持持续依赖于肿瘤和宿主细胞群之间的动态相互作用，通过肿瘤微环境中的信号分子和表面受体。这种相互作用决定了肿瘤生长的命运。这些信息，在这篇文章中描述和评估，提供了重要的新的见解，致癌的病因学和肿瘤的生长，侵袭和转移可能是治疗逮捕。以下关于癌症微环境的事实和概念，展示了现代分子研究结果如何揭示各种癌症疾病对整个个体的内部细胞，组织和器官环境的影响，以及这如何适用于设计新的工作以改善人类癌症诊断和治疗。本文讨论了几种特定类型的实验诱导和临床常见的癌症，以获得有助于解释肿瘤微环境中事件的原则，这些原则适用于一般癌症，特别是人类恶性疾病。
In normal tissues and organs, the activities of the constituent cells are strictly restricted to the tasks assigned to them during development. In addition they (with the exception of leukocytes) remain inflexibly confined to their territorial domains by regulatory interactions with their neighbors. This creates specialized local micro-environments in which structure and function are orderly, stable and tightly controlled by feed-back loops, within interacting regulatory networks. This system has considerable ability to adapt to changing conditions. In contrast, the microenvironment in regions where tumors are forming and expanding is characterized by progressive loss of specialized or differentiated cellular functions, disorderly molecular signals, degeneration of microscopical organ structure. This, coupled with the traffic of cells into and out of the tumor, often culminating in local invasion and metastasis to other organs. The nature of these disturbed molecular and cellular interactions is, by definition, highly unstable and increasingly unpredictable as time passes. It also varies between different tumors, sometimes even leading to regression. However, systematic analysis of this dysfunction in the tumor microcosm, using multiple modern research techniques, has revealed that all actively growing primary and secondary neoplasms share an absolute dependency upon support from adjacent non-neoplastic cells of the host. This support, in turn, continuously depends upon dynamic interplay between tumor and host cell populations, via signaling molecules and surface receptors in the tumor microenvironment. Such interplay determines the fate of the growing neoplasm. Such information, described and evaluated in this article, provides important new insights into the etiology of carcinogenesis and how tumor growth, invasion and metastasis might be therapeutically arrested. The facts and concepts assembled below, regarding the cancer microenvironment, demonstrate how modern molecular findings reveal the impact of the wide range of cancer diseases upon the internal cellular, tissue and organ environments of the whole individual and how this applies to designing new work to improve human cancer diagnosis and treatment. The article discusses several specific types of experimentally-induced and clinically common cancers to derive principles useful for interpreting events in the tumor microenvironment, which apply to cancers in general and especially to human malignant disease.