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Sci Rep ; 11(1): 6655, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758206

RESUMO

The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-ß1 (TGF-ß1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-ß1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs. Collectively, these novel findings suggest that the artificial 3D tumour displays a clear cell distribution and ECM deposition that resembles a tumour environment in vivo, suggesting an innovative biological model to study a human tumour.


Assuntos
Derme/citologia , Derme/metabolismo , Proteínas da Matriz Extracelular/biossíntese , Fibroblastos/metabolismo , Biomarcadores , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Células Cultivadas , Citocinas/metabolismo , Matriz Extracelular , Fibronectinas/metabolismo , Imunofluorescência , Humanos , Alicerces Teciduais
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