Tarin David
Moores UCSD Comprehensive Cancer Center and Department of Pathology, University of California, La Jolla, CA, 92093, USA,
Cancer Metastasis Rev. 2013 Dec;32(3-4):553-66. doi: 10.1007/s10555-013-9438-4.
Current cancer research focuses mainly upon the cancer cells in malignant tumours and is providing a growing database about aberrations in their genetic composition. However, tumours also contain non-cancerous host tissue, referred to as the stroma, which plays an active and indispensable role in tumour growth and influences the virulence of the neoplasm towards the host. Many cell types inhabit the stroma, amidst apparently inert fibrous and viscous matrix material, composed of complex polysaccharides, proteins and other molecules. Actually, all of these elements are in constant turnover, causing unpredictable evolution in the properties of the community. This article provides pathologic observations and data on reciprocal interactions between these stromal and neoplastic components of tumours and how they change during the course of the disease. Malignant progression depends upon dauntingly intricate communications between different specialised lineages within the cellular society, which enable rapid adaptation to changing circumstances. Opportunistic misuse of such communication networks enables tumour cells to recruit and incorporate adjacent normal stroma into their midst, so that they may grow, infiltrate and parasitise the host. The absolute dependency of primary tumours and metastases on their diverse stromal components for survival and their insatiable need to continuously recruit more stroma to support expansion, renders them vulnerable to strategies capable of disrupting the cellular interactions involved. This dependency is of critical importance for cancer therapy research, and proposed methods for turning this parasitic behaviour of tumours against themselves are suggested below.
当前癌症研究主要聚焦于恶性肿瘤中的癌细胞,并正在形成一个关于其基因组成异常的不断增长的数据库。然而,肿瘤中还包含非癌性的宿主组织,即基质,它在肿瘤生长中发挥着积极且不可或缺的作用,并影响肿瘤对宿主的毒性。许多细胞类型存在于基质中,其间是由复杂多糖、蛋白质和其他分子组成的看似惰性的纤维状和粘性基质材料。实际上,所有这些成分都在不断更新,导致群落特性发生不可预测的演变。本文提供了关于肿瘤的这些基质和肿瘤成分之间相互作用的病理学观察和数据,以及它们在疾病过程中如何变化。恶性进展取决于细胞社会中不同专门谱系之间极其复杂的通讯,这使得能够快速适应不断变化的环境。对这种通讯网络的机会主义滥用使肿瘤细胞能够招募相邻的正常基质并将其纳入其中,从而使其能够生长、浸润并寄生于宿主。原发性肿瘤和转移瘤对其多样的基质成分在生存方面的绝对依赖以及它们对持续招募更多基质以支持扩张的无尽需求,使它们容易受到能够破坏相关细胞相互作用的策略的影响。这种依赖性对癌症治疗研究至关重要,下面提出了一些利用肿瘤这种寄生行为来对抗肿瘤自身的方法。