How cancer-associated fibroblasts impact tumour metastasis and therapy response in breast cancer
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Abstract
Our research aims to identify novel strategies to target the tumour and/or stroma for the prevention or suppression of metastatic cancer and to overcome treatment-resistant tumour progression focusing on the role of normal and cancer-associated fibroblasts in breast and skin cancer.
Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types within the tumour microenvironment. Besides their matrix-remodelling capabilities and their role in
promoting primary tumour growth and metastasis, CAFs have been proposed to have immunosuppressive functions. However, high in vitro plasticity, high heterogeneity and a lack of specific markers hamper the functional analyses of CAFs.
By combining in vivo cancer and metastasis models with in vitro 2D/3D co-culture systems we address the role of fibroblasts in tumour progression, therapy response, but also how therapies themselves impact fibroblasts and their pro- and anti-tumorigenic phenotypes. Recently, we depicted the tumour-promoting role of the matrix-remodelling CAF receptor Endo180 (MRC2) and its function in breast cancer metastasis, CD8+ T-cell Infiltration and Immune-Checkpoint Blockade response.