BackgroundNumerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM), which represents the endothelial-independent formation of microvascular channels by cancer cells. However, the effect of vitamin D on VM formation in BC has not been thoroughly investigated. This study examined the impact of 1α,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, on the expression of major factors involved in BC migration, invasion, and VM formation.Experimental MethodsPublicly available transcriptomic datasets were used to profile the expression status of the key VM markers in vitamin D-treated BC cells. The in silico data were validated by examining the expression and activity of the key factors that are involved in tumor progression and MV formation in hormone-positive MCF-7 and aggressive triple‐negative MDA-MB-231 BC cells after treatment with calcitriol.Results and DiscussionsThe bioinformatics analysis showed that tumor VM formation-enriched pathways were differentially downregulated in vitamin D-treated cells when compared with control counterparts. Treatment of BC cells with calcitriol resulted in increased expression of tissue inhibitors of metalloproteinases (TIMPs 1 and 2) and decreased content and gelatinolytic activity of matrix metalloproteinases (MMPs 2 and 9). Furthermore, calcitriol treatment reduced the expression of several pro-MV formation regulators including vascular endothelial growth factor (VEGF), tumor growth factor (TGF-β1), and amphiregulin. Eventually, this process resulted in a profound reduction in cell migration and invasion following the treatment of BC cells with calcitriol when compared to the controls. Finally, the formation of VM was diminished in the aggressive triple‐negative MDA-MB-231 cancer cell line after calcitriol treatment.ConclusionOur findings demonstrate that vitamin D mediates its antitumor effects in BC cells by inhibiting and curtailing their potential for VM formation.

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The pertinence of the fiber element approach to enable thorough numerical investigation on the potential for progressive collapse of reinforced concrete (RC) frame structures owing to interior column exclusion is examined using twenty-nine RC sub-assemblages with five different test setups and three different test scales. A qualitative examination of the results reveals a good agreement between the test results and the outcomes of the fiber-element-based numerical model using the finite element package SeismoStruct. Moreover, minor discrepancies between the test and numerical data demonstrate the capability of the fiber-element-based model to accurately simulate the behavior of RC elements with various boundary conditions and scales under the context of progressive collapse. Given the costly nature of experimental research, test errors, and the lengthy testing process, the proposed numerical model based on the fiber element approach can be considered a viable option for analyzing structures under progressive collapse due to the interior column exclusion scenario. Engineers and researchers can use the conclusions and comments highlighted in the study as a guide to create accurate models for the analysis of RC structures subjected to progressive collapse.

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