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    Data are presented as mean ± SEM, as indicated in the legend of each figure. The significance of the differences between groups was evaluated using unpaired t test, p value < 0.05 was considered significant. Statistical parameters including the precision measures (mean ± SEM) and statistical significance are reported in the Figures and the Figure Legends when necessary. In figures, asterisks denote statistical significance (*, p < 0.05; **, p < 0.01; ***, p < 0.001), unless indicated otherwise. Experiments were repeated at least twice. Statistical analysis was performed in GraphPad PRISM 6.
    For microbiome analyses the statistical differences between the groups were estimated with non-parametric Mann-Whitney test, PERMANOVA test and p values were corrected for multiple tests using q-value 0.05 as a cutoff and data was visualized using heatmaps and PCA plots (Partek 6.6).
    The accession number for the raw data files for 16SRNA microbiome sequencing analysis reported in this paper is NCBI BioProject:
    Contents lists available at ScienceDirect
    Materials Today Chemistry
    Cellular morphologies, motility, and epithelialemesenchymal transition of breast cancer 78110-38-0 incubated on electrospun polymeric fiber substrates in hypoxia
    Advanced Polymeric Nanostructured Materials Engineering, Graduate School of Engineering, Toyota Technological Institute, 2-12-1 Hisakata, Tempaku, Nagoya 468 8511, Japan
    Article history:
    Received in revised form
    Available online 13 November 2018
    Polymeric fibers substrates
    Cancer cells
    Epithelialemesenchymal transition
    Gene expression
    Cellular motility
    Using polymeric fiber substrates with different mechanical features and surface topographies (fiber alignments) as microenvironment of cell culture substrates that influences cancer progression and metastatic potential, we have demonstrated systematically the effect of stiffness and topographies on two different types of breast cancer cells (MDA-MB-231 and MCF-7). The cells cultured on different substrates both normoxic and hypoxic conditions showed different morphologies, and these morpho-logical differences were correlated with cellular motility and gene expression. We discussed the effect of hypoxia on gene expression and cellular motility to understand the cellecell and cellesubstrate in-teractions. The progresses of microenvironment-mediated tumor progression in artificial extracellular matrix explored the design criteria to understand the cancer progression mechanism and metastatic potential.
    1. Introduction
    Cancer ranks as the leading cause of mortality in Japan. Fifty percent of the population is expected to suffer from cancer in their lifetime. In addition, in 2017, around 30% of deaths have been attributed to cancer, making it a major health problem [1]. Cancer morbidity and mortality in Japan are on the rise year by year, and more than 350,000 new deaths occur annually with an aging population and longevity [2]. With the increase in life ex-pectancy, it is predicted that cancer morbidity will continue to rise, placing a financial strain on healthcare systems to improve the quality of life.
    Breast cancer is one of the most common malignancies in women and has the higher incidence and mortality rates among all female malignant tumors [1,3]. The average 5-year survival rate of breast cancer is reported to be around 55% because of the poor outcome of the therapy for metastatic disease in resistance to ra-diation and chemotherapy [4]. The cancer therapies with poor prognosis prompt us to conduct a novel study on an effective cancer therapy. That is, breakthroughs in effective cancer therapies are
    * Corresponding author. r> E-mail address: [email protected] (M. Okamoto).
    imperative. The microenvironment of the tumor cells may play a vital role in such resistance because of the maintainable homeo-stasis by interacting with each other. The understanding of the interaction between microenvironment and cancer cells is also a critical subject to progress in the cancer treatment [5,6]. Cancer cells destroy the normal balance in the microenviron-ment. These disruptions induce proliferation, gene expression, and migration to promote cancer malignancy [7]. In addition, during cancer progression, cancer cells mainly reconstruct the aberrant extracellular matrix (ECM). The cells do not simply recreate the ECM, and the remodeled ECM provides biochemical and biophysi-cal cues to the neighboring cells (cancer cells and stromal cells) to promote cancer progression [8e11].