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

Kristiaan J. Lenos; Daniël M. Miedema; Sophie C. Lodestijn; Lisanne E. Nijman; Tom van den Bosch; Xavier Romero Ros; Filipe C. Lourenço; Maria C. Lecca; Maartje van der Heijden; Sanne M. van Neerven; Anita van Oort; Nicolas Leveille; Ronja S. Adam; Felipe de Sousa e Melo; Joy Otten; Patrick Veerman; Guillaume Hypolite; Lianne Koens; Scott K. Lyons; Giorgio Stassi; Douglas J. Winton; Jan Paul Medema; Edward Morrissey; Maarten F. Bijlsma; Louis Vermeulen

doi:https://doi.org/10.1038/s41556-018-0179-z

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

Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom van den Bosch, Xavier Romero Ros, Filipe C. Lourenço, Maria C. Lecca, Maartje van der Heijden, Sanne M. van Neerven, Anita van Oort, Nicolas Leveille, Ronja S. Adam, Felipe de Sousa e Melo, Joy Otten, Patrick Veerman, Guillaume Hypolite, Lianne Koens, Scott K. Lyons, Giorgio StassiDouglas J. Winton, Jan Paul Medema, Edward Morrissey, Maarten F. Bijlsma, Louis Vermeulen

Research output: Contribution to journal › Article › Academic › peer-review

122 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1193-1202
Journal	Nature cell biology
Volume	20
Issue number	10
DOIs	https://doi.org/10.1038/s41556-018-0179-z
Publication status	Published - 2018

Access to Document

https://doi.org/10.1038/s41556-018-0179-z

Cite this

Lenos, K. J., Miedema, D. M., Lodestijn, S. C., Nijman, L. E., van den Bosch, T., Romero Ros, X., Lourenço, F. C., Lecca, M. C., van der Heijden, M., van Neerven, S. M., van Oort, A., Leveille, N., Adam, R. S., de Sousa e Melo, F., Otten, J., Veerman, P., Hypolite, G., Koens, L., Lyons, S. K., ... Vermeulen, L. (2018). Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer. Nature cell biology, 20(10), 1193-1202. https://doi.org/10.1038/s41556-018-0179-z

@article{be80f855730d49d0b07c89b7fc543628,

title = "Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer",

abstract = "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.",

author = "Lenos, {Kristiaan J.} and Miedema, {Dani{\"e}l M.} and Lodestijn, {Sophie C.} and Nijman, {Lisanne E.} and {van den Bosch}, Tom and {Romero Ros}, Xavier and Louren{\c c}o, {Filipe C.} and Lecca, {Maria C.} and {van der Heijden}, Maartje and {van Neerven}, {Sanne M.} and {van Oort}, Anita and Nicolas Leveille and Adam, {Ronja S.} and {de Sousa e Melo}, Felipe and Joy Otten and Patrick Veerman and Guillaume Hypolite and Lianne Koens and Lyons, {Scott K.} and Giorgio Stassi and Winton, {Douglas J.} and Medema, {Jan Paul} and Edward Morrissey and Bijlsma, {Maarten F.} and Louis Vermeulen",

year = "2018",

doi = "https://doi.org/10.1038/s41556-018-0179-z",

language = "English",

volume = "20",

pages = "1193--1202",

journal = "Nature cell biology",

issn = "1465-7392",

publisher = "Nature Publishing Group",

number = "10",

}

Lenos, KJ, Miedema, DM, Lodestijn, SC, Nijman, LE, van den Bosch, T, Romero Ros, X, Lourenço, FC, Lecca, MC, van der Heijden, M, van Neerven, SM, van Oort, A, Leveille, N, Adam, RS, de Sousa e Melo, F, Otten, J, Veerman, P, Hypolite, G, Koens, L, Lyons, SK, Stassi, G, Winton, DJ, Medema, JP, Morrissey, E, Bijlsma, MF & Vermeulen, L 2018, 'Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer', Nature cell biology, vol. 20, no. 10, pp. 1193-1202. https://doi.org/10.1038/s41556-018-0179-z

TY - JOUR

T1 - Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer

AU - Lenos, Kristiaan J.

AU - Miedema, Daniël M.

AU - Lodestijn, Sophie C.

AU - Nijman, Lisanne E.

AU - van den Bosch, Tom

AU - Romero Ros, Xavier

AU - Lourenço, Filipe C.

AU - Lecca, Maria C.

AU - van der Heijden, Maartje

AU - van Neerven, Sanne M.

AU - van Oort, Anita

AU - Leveille, Nicolas

AU - Adam, Ronja S.

AU - de Sousa e Melo, Felipe

AU - Otten, Joy

AU - Veerman, Patrick

AU - Hypolite, Guillaume

AU - Koens, Lianne

AU - Lyons, Scott K.

AU - Stassi, Giorgio

AU - Winton, Douglas J.

AU - Medema, Jan Paul

AU - Morrissey, Edward

AU - Bijlsma, Maarten F.

AU - Vermeulen, Louis

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85053063179&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30177776

U2 - https://doi.org/10.1038/s41556-018-0179-z

DO - https://doi.org/10.1038/s41556-018-0179-z

M3 - Article

C2 - 30177776

SN - 1465-7392

VL - 20

SP - 1193

EP - 1202

JO - Nature cell biology

JF - Nature cell biology

IS - 10

ER -

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

Abstract

Access to Document

Other files and links

Cite this