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. 2017 Jul 29;9(8):98. doi: 10.3390/cancers9080098

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© 2017 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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EMT-induced spheroids as an in vitro model of stem cell niches and tumors. Spheroids can be obtained by aggregation and compaction (a) or spontaneous formation from monolayer cultures, mediated by activation of EMT related pathway and gene associated with adhesion and motility (b). Spheroids are globular and compact structures that can be handled without causing mechanical dissociation of the cells, characterized by a hypoxic core with quiescent cells surrounded by a rim of proliferating cells. The hypoxic gradient activates Notch and other EMT associated pathways favoring the maintenance of a “metastable” state of differentiation within the spheroid (c). Characteristics of normal tissue spheroids (d) and cancer spheroids (e). EMT: epithelial-to-mesenchymal transition; MET: mesenchymal-to-epithelial transition; TGF-β: Transforming Growth Factor-beta; EGR-1: Early growth response protein 1.