PT  - JOURNAL ARTICLE
AU  - Ute Jungwirth
AU  - Antoinette van Weverwijk
AU  - Liam Jenkins
AU  - John Alexander
AU  - David Vicente
AU  - Qiong Gao
AU  - Syed Haider
AU  - Marjan Iravani
AU  - Clare M. Isacke
TI  - Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis
AID  - 10.1101/2020.05.17.100412
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.17.100412
4099  - http://biorxiv.org/content/early/2020/05/17/2020.05.17.100412.short
4100  - http://biorxiv.org/content/early/2020/05/17/2020.05.17.100412.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.