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

共 46 条

[21] Fast and accurate short read alignment with Burrows-Wheeler transform [J].

Li, Heng ;

Durbin, Richard .

BIOINFORMATICS, 2009, 25 (14) :1754-1760

[22] Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors [J].

Li, Huipeng ;

Courtois, Elise T. ;

Sengupta, Debarka ;

Tan, Yuliana ;

Chen, Kok Hao ;

Goh, Jolene Jie Lin ;

Kong, Say Li ;

Chua, Clarinda ;

Hon, Lim Kiat ;

Tan, Wah Siew ;

Wong, Mark ;

Choi, Paul Jongjoon ;

Wee, Lawrence J. K. ;

Hillmer, Axel M. ;

Tan, Iain Beehuat ;

Robson, Paul ;

Prabhakar, Shyam .

NATURE GENETICS, 2017, 49 (05) :708-+

[23] featureCounts: an efficient general purpose program for assigning sequence reads to genomic features [J].

Liao, Yang ;

Smyth, Gordon K. ;

Shi, Wei .

BIOINFORMATICS, 2014, 30 (07) :923-930

[24] Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A [J].

Lotti, Fiorenza ;

Jarrar, Awad M. ;

Pai, Rish K. ;

Hitomi, Masahiro ;

Lathia, Justin ;

Mace, Adam ;

Gantt, Gerald A., Jr. ;

Sukhdeo, Kumar ;

DeVecchio, Jennifer ;

Vasanji, Amit ;

Leahy, Patrick ;

Hjelmeland, Anita B. ;

Kalady, Matthew F. ;

Rich, Jeremy N. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (13) :2851-2872

[25] Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes [J].

Marusyk, Andriy ;

Tabassum, Doris P. ;

Janiszewska, Michalina ;

Place, Andrew E. ;

Trinh, Anne ;

Rozhok, Andrii I. ;

Pyne, Saumyadipta ;

Guerriero, Jennifer L. ;

Shu, Shaokun ;

Ekram, Muhammad ;

Ishkin, Alexander ;

Cahill, Daniel P. ;

Nikolsky, Yuri ;

Chan, Timothy A. ;

Rimawi, Mothaffar F. ;

Hilsenbeck, Susan ;

Schiff, Rachel ;

Osborne, Kent C. ;

Letai, Antony ;

Polyak, Kornelia .

CANCER RESEARCH, 2016, 76 (22) :6495-6506

[26] The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse [J].

Merlos-Suarez, Anna ;

Barriga, Francisco M. ;

Jung, Peter ;

Iglesias, Mar ;

Virtudes Cespedes, Maria ;

Rossell, David ;

Sevillano, Marta ;

Hernando-Momblona, Xavier ;

da Silva-Diz, Victoria ;

Munoz, Purificacion ;

Clevers, Hans ;

Sancho, Elena ;

Mangues, Ramon ;

Batlle, Eduard .

CELL STEM CELL, 2011, 8 (05) :511-524

[27] Dclk1 distinguishes between tumor and normal stem cells in the intestine [J].

Nakanishi, Yuki ;

Seno, Hiroshi ;

Fukuoka, Ayumi ;

Ueo, Taro ;

Yamaga, Yuichi ;

Maruno, Takahisa ;

Nakanishi, Naoko ;

Kanda, Keitaro ;

Komekado, Hideyuki ;

Kawada, Mayumi ;

Isomura, Akihiro ;

Kawada, Kenji ;

Sakai, Yoshiharu ;

Yanagita, Motoko ;

Kageyama, Ryoichiro ;

Kawaguchi, Yoshiya ;

Taketo, Makoto M. ;

Yonehara, Shin ;

Chiba, Tsutomu .

NATURE GENETICS, 2013, 45 (01) :98-U143

[28] A human colon cancer cell capable of initiating tumour growth in immunodeficient mice [J].

O'Brien, Catherine A. ;

Pollett, Aaron ;

Gallinger, Steven ;

Dick, John E. .

NATURE, 2007, 445 (7123) :106-110

[29] Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown [J].

Pertea, Mihaela ;

Kim, Daehwan ;

Pertea, Geo M. ;

Leek, Jeffrey T. ;

Salzberg, Steven L. .

NATURE PROTOCOLS, 2016, 11 (09) :1650-1667

[30] StringTie enables improved reconstruction of a transcriptome from RNA-seq reads [J].

Pertea, Mihaela ;

Pertea, Geo M. ;

Antonescu, Corina M. ;

Chang, Tsung-Cheng ;

Mendell, Joshua T. ;

Salzberg, Steven L. .

NATURE BIOTECHNOLOGY, 2015, 33 (03) :290-+

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