Background Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behavior. Herein we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex-vivo patients derived explants (PDEs), we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome. Methods Fifty patients (31 non-IBC; 19 IBC) were enrolled in the present study. To test their validation in clinical studies, PDEs were cultured as an ex-vivo model. Gene expression and cytokine array were used to identify candidate genes and cytokines contributing to metastasis in the examined fresh tissues and PDEs. Bioinformatics analysis was applied on identified differentially expressed genes (DEGs) using GeneMANIA and Metascape gene annotation and analysis resource to identify pathways involved in IBC metastasis. Results Normal and cancer fresh tissues and PDEs of IBC were characterized by overexpression of CDH1 and MMP14 and downregulation of CTNNA1 and TIMP1 compared to non-IBC. The secretome of IBC cancer PDEs is characterized by significantly high expression of interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared to non-IBC. Conclusion Genes expressed by adhisome and matrisome play a significant role in IBC metastasis and should be considered novel target therapy.
Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.
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The current study aimed to establish an efficient in vitro propagation and conservation protocol for Brunfelsia pauciflora plant. The effect of plant growth regulators types (BAP, Kin, 2ip and NAA) and concentrations at 0.0, 1.0, and 2.0 mg/l were studied during establishment phase in comparing with hormonal-free medium. In vitro proliferated shootlets were encapsulated using various levels of sodium alginate at 1, 2 and 3% (W/V) and calcium chloride at 2.5,5 and 10 %. Regrowth ability of encapsulated explants was evaluated after conservation for 3, 5, and 7 weeks and compared with non-encapsulated buds. The findings of the current study proved that during establishment phase, applying BAP at 2.0 mg/l gave the best results during the three successive subcultures. The best treatment 2ip (2.0mg/l) + BAP (2.0mg/l) + NAA (2.0mg/l) that was considered ideal propagation protocol for shooting and rooting of Brunfelsia. Successful plant recovery from encapsulated explants using low concentrations of sodium alginate (1%) and calcium chloride at 2.5%, proved that the explants could to be survive at highest percent (100%) during conservation periods 3, 5 and 7weeks. Increasing calcium chloride to 5% with the same concentration of sodium alginate (1%) caused gradually reduced percent of survival to 53.33% with increasing conservations period (from 3 to 7weeks). It is the first paper of the application of syndetic seed technique on Brunfelsia for the shortest period conservation and successive renovation of shootlets whose genetic stabilization was evaluated by analysis of RAPD that proved that the genetic similarity ranged from 56.1 to 80%. These results were confirmed by anatomical sections made in Brunfelsia leaf blade.
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