Cell competition promotes metastatic intestinal cancer through a multistage process

A Krotenberg Garcia; M Ledesma-Terrón; M Lamprou; J Vriend; ME van Luyk; SJE Suijkerbuijk

doi:10.1016/j.isci.2024.109718

Cell competition promotes metastatic intestinal cancer through a multistage process

A Krotenberg Garcia, M Ledesma-Terrón, M Lamprou, J Vriend, ME van Luyk, SJE Suijkerbuijk^*

^*Corresponding author for this work

Utrecht University

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

Abstract

Cell competition plays an instrumental role in quality control during tissue development and homeostasis. Nevertheless, cancer cells can exploit this process for their own proliferative advantage. In our study, we generated mixed murine organoids and microtissues to explore the impact of cell competition on liver metastasis. Unlike competition at the primary site, the initial effect on liver progenitor cells does not involve the induction of apoptosis. Instead, metastatic competition manifests as a multistage process. Initially, liver progenitors undergo compaction, which is followed by cell-cycle arrest, ultimately forcing differentiation. Subsequently, the newly differentiated liver cells exhibit reduced cellular fitness, rendering them more susceptible to outcompetition by intestinal cancer cells. Notably, cancer cells leverage different interactions with different epithelial populations in the liver, using them as scaffolds to facilitate their growth. Consequently, tissue-specific mechanisms of cell competition are fundamental in driving metastatic intestinal cancer.

Original language	English
Article number	109718
Number of pages	21
Journal	iScience
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.isci.2024.109718
Publication status	Published - 17 May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Funding

We thank Ilya Grigoriev and the Biology Imaging Center of Utrecht University Center for technical support with imaging; members of the Division of Developmental Biology, Dimitrios Laskaris for input and technical support. Jacco van Rheenen for input and critically reading the article. This work was financially supported by Dutch Cancer Society Young Investigator Grant 11491/2018-1 (to S.J.E.S.) and Ayudas Margarita Salas para la formaci\u00F3n de j\u00F3venes doctores CA4/RSUE/2022-00236 (to M.L.T.). Conceptualization, A.K.G. and S.J.E.S.; methodology, A.K.G. M.L.T. and S.J.E.S.; software, M.L.T.; formal analysis, A.K.G. and M.L.T.; investigation, A.K.G. M.L.T. M.L. J.V. and M.v.L.; writing \u2013 original draft, A.K.G. and S.J.E.S.; writing \u2013 review & editing, A.K.G. and S.J.E.S.; visualization, A.K.G. and S.J.E.S.; funding acquisition, M.L.T. and S.J.E.S.; supervision, S.J.E.S. The authors declare no competing interests. During the preparation of this work the authors used GPT-3.5/OpenAI in order to improve the readability of the methods section. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Funders	Funder number
Division of Developmental Biology
KWF Kankerbestrijding	CA4/RSUE/2022-00236, 11491/2018-1

Keywords

(low fitness) Cancer
Differentiation
Intestinal cancer cells
Organoid state

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2024.109718Licence: CC BY

PIIS2589004224009404Final published version, 6.02 MBLicence: CC BY

Cite this

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title = "Cell competition promotes metastatic intestinal cancer through a multistage process",

abstract = "Cell competition plays an instrumental role in quality control during tissue development and homeostasis. Nevertheless, cancer cells can exploit this process for their own proliferative advantage. In our study, we generated mixed murine organoids and microtissues to explore the impact of cell competition on liver metastasis. Unlike competition at the primary site, the initial effect on liver progenitor cells does not involve the induction of apoptosis. Instead, metastatic competition manifests as a multistage process. Initially, liver progenitors undergo compaction, which is followed by cell-cycle arrest, ultimately forcing differentiation. Subsequently, the newly differentiated liver cells exhibit reduced cellular fitness, rendering them more susceptible to outcompetition by intestinal cancer cells. Notably, cancer cells leverage different interactions with different epithelial populations in the liver, using them as scaffolds to facilitate their growth. Consequently, tissue-specific mechanisms of cell competition are fundamental in driving metastatic intestinal cancer.",

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AU - Ledesma-Terrón, M

AU - Lamprou, M

AU - Vriend, J

AU - van Luyk, ME

AU - Suijkerbuijk, SJE

PY - 2024/5/17

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N2 - Cell competition plays an instrumental role in quality control during tissue development and homeostasis. Nevertheless, cancer cells can exploit this process for their own proliferative advantage. In our study, we generated mixed murine organoids and microtissues to explore the impact of cell competition on liver metastasis. Unlike competition at the primary site, the initial effect on liver progenitor cells does not involve the induction of apoptosis. Instead, metastatic competition manifests as a multistage process. Initially, liver progenitors undergo compaction, which is followed by cell-cycle arrest, ultimately forcing differentiation. Subsequently, the newly differentiated liver cells exhibit reduced cellular fitness, rendering them more susceptible to outcompetition by intestinal cancer cells. Notably, cancer cells leverage different interactions with different epithelial populations in the liver, using them as scaffolds to facilitate their growth. Consequently, tissue-specific mechanisms of cell competition are fundamental in driving metastatic intestinal cancer.

AB - Cell competition plays an instrumental role in quality control during tissue development and homeostasis. Nevertheless, cancer cells can exploit this process for their own proliferative advantage. In our study, we generated mixed murine organoids and microtissues to explore the impact of cell competition on liver metastasis. Unlike competition at the primary site, the initial effect on liver progenitor cells does not involve the induction of apoptosis. Instead, metastatic competition manifests as a multistage process. Initially, liver progenitors undergo compaction, which is followed by cell-cycle arrest, ultimately forcing differentiation. Subsequently, the newly differentiated liver cells exhibit reduced cellular fitness, rendering them more susceptible to outcompetition by intestinal cancer cells. Notably, cancer cells leverage different interactions with different epithelial populations in the liver, using them as scaffolds to facilitate their growth. Consequently, tissue-specific mechanisms of cell competition are fundamental in driving metastatic intestinal cancer.

KW - (low fitness) Cancer

KW - Differentiation

KW - Intestinal cancer cells

KW - Organoid state

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Cell competition promotes metastatic intestinal cancer through a multistage process

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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