Interactions between cancer stem cells and their niche govern metastatic colonization

被引:1055
作者
Malanchi, Ilaria [1 ,2 ]
Santamaria-Martinez, Albert [1 ,2 ]
Susanto, Evelyn [1 ,2 ]
Peng, Hong [1 ,2 ,3 ]
Lehr, Hans-Anton [4 ]
Delaloye, Jean-Francois [5 ]
Huelsken, Joerg [1 ,2 ]
机构
[1] Swiss Inst Expt Canc Res, Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland
[2] Natl Ctr Competence Res Mol Oncol, CH-1015 Lausanne, Switzerland
[3] So Med Univ, Nanfang Hosp, Dept Otorhinolaryngol Head & Neck Surg, Guangzhou 510515, Guangdong, Peoples R China
[4] Univ Lausanne, CHUV, Univ Inst Pathol, CH-1011 Lausanne, Switzerland
[5] CHU Vaudois, Dept Obstet & Gynecol, CH-1011 Lausanne, Switzerland
关键词
TUMOR-INITIATING CELLS; PERIOSTIN-NULL MICE; BREAST-CANCER; MAMMARY-TUMORS; BETA-CATENIN; MOUSE MODEL; LONG-TERM; EXPRESSION; IDENTIFICATION; DISSEMINATION;
D O I
10.1038/nature10694
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps(1). Although dissemination of tumour cells seems to be an early and frequent event(2), 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 sites(3,4). Prevalent target sites are characteristic of many tumour entities(5), 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.
引用
收藏
页码:85 / U95
页数:7
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