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Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis

Lookup NU author(s): Dr Ute JungwirthORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2021, The Author(s). Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serial in vivo passage for its ability to overcome these stromal defects provides important insight into, how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation.

Publication metadata

Author(s): Jungwirth U, van Weverwijk A, Evans RJ, Jenkins L, Vicente D, Alexander J, Gao Q, Haider S, Iravani M, Isacke CM

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Online publication date: 10/06/2021

Acceptance date: 26/04/2021

Date deposited: 13/02/2024

ISSN (electronic): 2041-1723

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41467-021-23583-1

DOI: 10.1038/s41467-021-23583-1

PubMed id: 34112782

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