Cell Stem Cell:肿瘤干细胞在肿瘤转移中的作用
2012-03-09 MedSci 生物谷Bioon.com
近日,国际权威刊物《细胞》杂志子刊《细胞—干细胞》Cell Stem Cell以Preview的形式发表了欧阳高亮教授课题组的研究文章“Periostin:a bridge between cancer stem cells and their metastatic niche”的评论性文章,对2012年1月Huelsken J.教授发表在国际权威刊物《自然》上的研究论文“Interactions
近日,国际权威刊物《细胞》杂志子刊《细胞—干细胞》Cell Stem Cell以Preview的形式发表了欧阳高亮教授课题组的研究文章“Periostin:a bridge between cancer stem cells and their metastatic niche”的评论性文章,对2012年1月Huelsken J.教授发表在国际权威刊物《自然》上的研究论文“Interactions between cancer stem cells and their niche govern metastatic colonization”进行了专题评论。
众所周知,肿瘤转移是肿瘤致死的主要原因。目前研究发现,肿瘤干细胞在肿瘤发生以及肿瘤转移、耐药、复发等过程中均起关键作用,而肿瘤干细胞微环境则在肿瘤干细胞干性维持、分化以及肿瘤发生发展中发挥至关重要的调控功能。因此揭示肿瘤干细胞与其微环境之间的相互作用及其分子机理,将深化人们对肿瘤发生发展规律的认识,并可能为针对肿瘤转移提供重要的作用靶点。
Huelsken J.教授课题组的研究发现,细胞外基质分泌蛋白Periostin在小鼠乳腺癌肿瘤干细胞的干性维持以及小鼠乳腺癌肺转移中起着关键性的调控作用。欧阳高亮教授课题组在评论中首先对肿瘤转移以及肿瘤干细胞在肿瘤转移中的作用进行了简要综述,然后结合本课题组有关Periostin蛋白在人结肠癌肝转移和人肿瘤干细胞干性调控中的功能等相关工作对Huelsken J.教授的这项研究进行了扼要回顾并给予了高度评价,同时对Periostin等细胞外基质蛋白在肿瘤干细胞及其微环境中的功能提出了自己的见解
doi:10.1016/j.stem.2012.01.002
Periostin: A Bridge between Cancer Stem Cells and Their Metastatic Niche
Zhe Wang, Gaoliang Ouyang
Only a minority of cancer cells have the potential to initiate metastatic growth, but the factors that limit metastatic colonization remain mostly unknown. Malanchi et al., 2012 recently demonstrated that stromal periostin is crucial for metastatic colonization by regulating the interactions between breast cancer stem cells and their metastatic niche.
doi:10.1038/nature10694
Interactions between cancer stem cells and their niche govern metastatic colonization
Ilaria Malanchi,1, 5 Albert Santamaria-Martínez,1, 5 Evelyn Susanto,1 Hong Peng,1, 2 Hans-Anton Lehr,3 Jean-Francois Delaloye4 & Joerg Huelsken1
Metastatic 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.
作者:MedSci
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