肿瘤干细胞与转移--Interactions between cancer stem cells and their niche govern

gandanxiaoyang

Nature：阻断periostin蛋白能阻止肿瘤干细胞启动肿瘤转移作者：towersimper 来源：生物谷 2011-12-12 11:28:08
" m4 U" C% h# Q6 v/ v/ }转移瘤(即原发性肿瘤细胞转移到新位点上形成的肿瘤)的增殖经常是肿瘤导致的并发症和死亡的主要原因。来自瑞士洛桑理工大学瑞士实验癌症研究中心的研究小组第一次非常密切地研究这些转移瘤本身的发展，而不是集中注意在它们起源的原发性肿瘤(primary cancer)，分离出一种在转移瘤发展中发挥关键中心的蛋白，并且证实阻断这种蛋白能够阻止继发性肿瘤(secondary cancer)的形成。2011年12月7日，他们的研究成果提前在线发表在《自然》期刊上，为治疗晚期阶段癌症打开新的治疗方案之门。
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! `, [) g& @1 M' H2 oMetastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps1. Although dissemination of tumour cells seems to be an early and frequent event2, the successful initiation of metastatic growth, a process termed ‘metastatic colonization’, is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites3, 4. Prevalent target sites are characteristic of many tumour entities5, suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.

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