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bioRxiv · 10.1101/2020.05.05.070607

Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer

Venning, F. A.·Zornhagen, K. W.·Wullkopf, L.·Hajkarim, M. C.·Won, K. J.·Madsen, C. D.·Erler, J. T.
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Abstract

Cancer-associated fibroblasts (CAFs) comprise a heterogeneous population of stromal cells within the tumour microenvironment. CAFs exhibit both tumour-promoting and tumour-suppressing functions, making them exciting targets for improving cancer treatments. A careful identification and characterisation of the CAF heterogeneity is thus necessary before implementing CAF-targeted strategies in cancer. With that in mind, we developed a flow cytometry strategy based on exclusion of non-CAF cells and successfully employed it to explore the temporal heterogeneity of CAFs in two models of triple-negative breast cancer (4T1 and 4T07). Analysing 128 murine tumours we identified 5-6 main CAF subpopulations and numerous minor ones based on the analysis of alpha smooth muscle actin, fibroblast activation protein alpha, platelet derived growth factor receptor alpha and beta, CD26/DPP4 and podoplanin. All markers showed temporal changes, and CD26+ CAFs emerged as a large novel subpopulation. These results form the foundation needed for the future elucidation of tumour-promoting CAF subpopulations.

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Venning, F. A., Zornhagen, K. W., Wullkopf, L., Hajkarim, M. C., Won, K. J., Madsen, C. D., Erler, J. T.. 2020-05-06. Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer. https://doi.org/10.1101/2020.05.05.070607

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