Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer

被引：132

作者：

Lenos, Kristiaan J. ^{[1
,2
]}

Miedema, Daniel M. ^{[1
,2
]}

Lodestijn, Sophie C. ^{[1
,2
]}

Nijman, Lisanne E. ^{[1
,2
]}

van den Bosch, Tom ^{[1
,2
]}

Ros, Xavier Romero ^{[1
,2
]}

Lourenco, Filipe C. ^{[3
]}

Lecca, Maria C. ^{[1
,2
]}

van der Heijden, Maartje ^{[1
,2
]}

van Neerven, Sanne M. ^{[1
,2
]}

van Oort, Anita ^{[1
,2
]}

Leveille, Nicolas ^{[1
,2
]}

Adam, Ronja S. ^{[1
,2
]}

Melo, Felipe de Sousa E. ^{[4
]}

Otten, Joy ^{[1
,2
]}

Veerman, Patrick ^{[1
,2
]}

Hypolite, Guillaume ^{[1
,2
]}

Koens, Lianne ^{[5
]}

Lyons, Scott K. ^{[6
]}

Stassi, Giorgio ^{[7
]}

Winton, Douglas J. ^{[3
]}

Medema, Jan Paul ^{[1
,2
]}

Morrissey, Edward ^{[8
]}

Bijlsma, Maarten F. ^{[1
,2
]}

Vermeulen, Louis ^{[1
,2
]}

机构：

[1] Univ Amsterdam, Amsterdam UMC, LEXOR, Ctr Expt & Mol Med,Canc Ctr Amsterdam, Amsterdam, Netherlands

[2] Amsterdam Gastroenterol & Metab, Amsterdam, Netherlands

[3] Univ Cambridge, Cambridge Inst, Canc Res UK, Cambridge, England

[4] Genentech Inc, Dept Discovery Oncol, San Francisco, CA USA

[5] Acad Med Ctr, Dept Pathol, Amsterdam, Netherlands

[6] Cold Spring Harbor Lab, Preclin Imaging, POB 100, Cold Spring Harbor, NY 11724 USA

[7] Univ Palermo, Dept Surg & Oncol Sci, Cellular & Mol Pathophysiol Lab, Palermo, Italy

[8] Univ Oxford, John Radcliffe Hosp, MRC, Weatherall Inst Mol Med, Oxford, England

来源：

NATURE CELL BIOLOGY | 2018年 / 20卷 / 10期

基金：

欧洲研究理事会;

关键词：

WNT ACTIVITY; REVEALS; HOMEOSTASIS; DYNAMICS; GROWTH; FIBROBLASTS; STRINGTIE; PREDICTS; MARKER; LEVEL;

D O I：

10.1038/s41556-018-0179-z

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem cell properties change in time depending on the cell location. Furthermore, although chemotherapy enriches for cells with a CSC phenotype, in this context functional stem cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

引用

页码：1193 / +

页数：12

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