Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression
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10.1016/j.biomaterials.2015.11.030
Inclou dades d'ús des de 2022
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hdl:2117/346059
Tipus de documentArticle
Data publicació2016-02
Condicions d'accésAccés obert
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Abstract
3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds.
Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term
monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the
tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were
microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for
15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating
distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of proinflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cellecell contacts and polarised around small lumina in the interior of the aggregates. Over the
culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss
of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures.
These phenotypic alterations, typical of advanced stages of cancer, were not observed in the monocultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma
crosstalk, disease progression and drug resistance mechanisms.
CitacióGualda Manzano, E.J. [et al.]. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression. "Biomaterials", Febrer 2016, vol. 78, p. 50-61.
ISSN0142-9612
Versió de l'editorhttps://www.sciencedirect.com/science/article/pii/S0142961215009345
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