Liver Research Group, Section of Oncology, School of Medicine, Royal Hallamshire Hospital, The University of Sheffield, Sheffield, UK.
Hepatol Res. 2010 Jan 1;40(1):83-94. doi: 10.1111/j.1872-034X.2009.00578.x. Epub 2009 Sep 25.
Colorectal cancer is one of the commonest malignancies in the "developed" world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines. Subsequently, colorectal metastasising cells are destroyed either by KC-performed phagocytosis or via the stimulation of other immune cells which migrate into the sinusoids and act accordingly. On the contrary, KC products, including cytokines, growth factors and matrix-degrading enzymes may promote liver metastasis, supporting tumour cell extravasation, motility and invasion. Current research aims to exploit the antineoplastic properties of KCs in new therapeutic approaches of colorectal cancer liver metastasis. Numerous agents, such as the granulocyte macrophage-colony stimulating factor, interferon gamma, muramyl peptide analogues and various antibody based treatments, have been tested in experimental models with promising results. Future trials may investigate their use in everyday clinical practice and compare their therapeutic value with current treatment of the disease.
结直肠癌是“发达”世界中最常见的恶性肿瘤之一。肝脏是其远处转移的主要宿主器官，当转移发生时，预示着疾病预后不良。库普弗细胞（KCs）是驻留在肝脏内的巨噬细胞，构成了针对通过门静脉循环到达肝窦的多种有害因子的有效第一道防线。KCs 清除化学化合物和死亡或受损细胞，消灭细菌并防止入侵的肿瘤细胞。它们可能通过释放多种细胞因子和趋化因子发挥关键的杀肿瘤作用，发挥细胞毒性和细胞抑制功能。随后，结直肠转移细胞要么被 KC 吞噬作用破坏，要么通过迁移到窦状隙并相应作用的其他免疫细胞的刺激而被破坏。相反，KC 产物，包括细胞因子、生长因子和基质降解酶，可能促进肝转移，支持肿瘤细胞的渗出、迁移和侵袭。目前的研究旨在利用 KCs 的抗肿瘤特性，为结直肠癌肝转移的新治疗方法提供依据。已经在实验模型中测试了许多药物，如粒细胞-巨噬细胞集落刺激因子、干扰素 γ、 muramyl 肽类似物和各种基于抗体的治疗方法，结果令人鼓舞。未来的试验可能会研究它们在日常临床实践中的应用，并将其治疗价值与目前的疾病治疗方法进行比较。
