Giakoustidis Alexandros, Mudan Satvinder, Hagemann Thorsten
Barts Cancer Institute, Queen Mary School of Medicine and Dentistry, University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.
The London Clinic, 116 Harley Street, London, W1G 7JL, UK.
Cancer Microenviron. 2015 Dec;8(3):177-86. doi: 10.1007/s12307-014-0155-5. Epub 2014 Oct 3.
The tumour microenvironment (TME) represents a dynamic network that plays an important role in tumour initiation, proliferation, growth, and metastasis. Cell behaviour may be regulated by interplay of molecular interactions involving positive and negative reinforcement as well as a high level of cross-talk, which determines this system. Additionally, cancer involves cell proliferation, its malignancy defined by the tumour's ability to break down normal tissue architecture and by a dynamic process of invasion and metastasis. The metastatic cascade is regulated by a chain of molecular steps which triggers the progression of the developing cancer cell in the primary tumour into a number of transformations, leading to invasion and proceeding to metastases. Tumour-associated macrophages (TAMs) play a key-role in the progression from inflammatory conditions to cancer; TAMs are also capable of infiltrating the tumour microenvironment. Furthermore, myeloid-derived suppressor cells (MDSCs), a population of inhibitory immune cells, have been reported to increase in various cancer types, although characterising human MDSCs remains difficult, as their phenotype is quite variable. The future of cancer treatment is likely to involve creating more drugs that target these elements as well as others. An overview of the tumour's microenvironment is, therefore, presented in this paper, focusing on the metastatic pathways of primary colorectal cancer to the liver.
肿瘤微环境(TME)是一个动态网络,在肿瘤的起始、增殖、生长和转移中起重要作用。细胞行为可能受分子相互作用的影响,这些相互作用涉及正反馈和负反馈以及高水平的相互交流,从而决定了这个系统。此外,癌症涉及细胞增殖,其恶性程度由肿瘤破坏正常组织结构的能力以及侵袭和转移的动态过程来定义。转移级联反应由一系列分子步骤调控,这些步骤触发原发性肿瘤中正在发展的癌细胞发生一系列转变,导致侵袭并进而发生转移。肿瘤相关巨噬细胞(TAM)在从炎症状态发展到癌症的过程中起关键作用;TAM也能够浸润肿瘤微环境。此外,髓系来源的抑制细胞(MDSC)是一类抑制性免疫细胞,据报道在各种癌症类型中数量都会增加,尽管对人类MDSC进行特征描述仍然很困难,因为它们的表型变化很大。癌症治疗的未来可能涉及研发更多针对这些以及其他因素的药物。因此,本文将概述肿瘤微环境,重点关注原发性结直肠癌向肝脏的转移途径。