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Cancer‐cell phenotype is not only the result of malignant progression, but also dependent on the microenvironment surrounding them, including influences from the extracellular matrix and its structural properties. We have investigated the influence of the nanofiber matrix of the self‐assembling peptide, RADA16, in comparison with collagen I and Matrigel on the malignant phenotype of the human breast‐cancer cell, MDA‐MB‐231, in 3D cultures, including the morphology, survival, proliferation rate, migration potential and the effect of these matrices on the malignancy of the cancer cells in vivo. Our data indicate that these tumor cells change their morphology in response to the different 3D matrix in vitro cultures and the RADA16 self‐assembling peptide scaffold mimics an extracellular matrix and could effectively reduce the malignant phenotype of the tumor cells in vitro and in vivo.

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