Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer
| Autor: | Kamilla Westarp Zornhagen, Chris D. Madsen, Kyoung-Jae Won, Lena Wullkopf, Freja Albjerg Venning, Morteza Chalabi Hajkarim, Janine Tera Erler |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Stromal cell medicine.diagnostic_test Platelet-Derived Growth Factor Receptor Alpha Cancer Alpha (ethology) Biology medicine.disease Flow cytometry 03 medical and health sciences 0302 clinical medicine Breast cancer Fibroblast activation protein alpha Podoplanin 030220 oncology & carcinogenesis Cancer research medicine 030304 developmental biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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