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. 2019 Aug 22;9:12263. doi: 10.1038/s41598-019-48701-4

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Cells cultured in the scaffold exhibit aggressive features. (a) Whole body IVIS imaging and percentage of mice with detectable tumors after 1 week from the orthotopic injection of MDA-MB-231 cultured in monolayer (2D) or in the scaffold (3D). (b) Tumor volume of mice with orthotopic injection of 2D and 3D cultured MDA-MB-231. Data represent mean ± S.E.M (n = 5) *p < 0.05. (c) Representative images of Cd31 stained histological sections, number of vessel for mm², and vessel area for mm² in xenograft tumors generated by orthotopic injection of 2D and 3D cultured MDA-MB-231. Cd31 positive cells (green) and nuclei stained with DAPI (blue). Scale bars: 300 µm. Data represent mean ± S.D. (n = 3). (d) Heatmap visualization of relative expression values of biomarkers related to tumor aggressiveness in MCF-7 and MDA-MB-231 in monolayer culture or within the scaffold. (e) Relative expression levels of LOX in MCF-7 and MDA-MB-231 within the scaffold versus monolayer cultures on days 1, 3 and 7. (f) Relative expression levels of LOX in breast cancer patients. *p < 0.01, two-sample Wilcoxon rank-sum test. (g) ROC curve of LOX accuracy as prognostic factor in patients with breast cancer.