Browsing by Author "Woodward, Wendy A"

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    Differential gene expression of Fresh Tissue and Patient-Derived Explants' Matricellular Proteins Augment Inflammatory Breast Cancer Metastasis: The Possible Role of IL-6 and MCP-1.
    (Dove Medical Press Ltd., 2023-01) Tarek, Alshaimaa; Mohamed, Hossam Taha; El-Sharkawy, Aya Ali; El-Sayed, Shrouk Khalaf; Hirshon, Jon Mark; Woodward, Wendy A; El-Shinawi, Mohamed; Mohamed, Mona Mostafa
    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.
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    IL-8 and MCP-1/CCL2 regulate proteolytic activity in triple negative inflammatory breast cancer a mechanism that might be modulated by Src and Erk1/2
    (Academic Press Inc., 8/15/2020) Taha Mohamed, Hossam; El-Ghonaimy, Eslam A; El-Shinawi, Mohamed; Hosney, Mohamed; Götte, Martin; Woodward, Wendy A; El-Mamlouk, Tahani; Mostafa Mohamed, Mona
    Inflammatory breast cancer (IBC) is a highly metastatic and lethal breast cancer. As many as 25–30% of IBCs are triple negative (TN) and associated with low survival rates and poor prognosis. We found that the microenvironment of IBC is characterized by high infiltration of tumor associated macrophages (TAMs) and by over-expression of the cysteine protease cathepsin B (CTSB). TAMs in IBC secrete high levels of the cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared to non-IBC patients. Herein, we tested the roles of IL-8 and MCP-1/CCL2 in modulating proteolytic activity and invasiveness of TN-non-IBC as compared to TN-IBC and addressed the underlying molecular mechanism(s) for both cytokines. Quantitative real time PCR results showed that IL-8 and MCP-1/CCL2 were significantly overexpressed in tissues of TN-IBCs. IL-8 and MCP-1/CCL2 induced CTSB expression and activity of the p-Src and p-Erk1/2 signaling pathways relevant for invasion and metastasis in TN-non-IBC, HCC70 cells and TN-IBC, SUM149 cells. Dasatinib, an inhibitor of p-Src, and U0126, an inhibitor of p-Erk1/2, down-regulated invasion and expression of CTSB by HCC70 and SUM149 cells, a mechanism that is reversed by IL-8 and MCP-1/CCL2. Our study shows that targeting the cytokines IL-8 and MCP-1/CCL2 and associated signaling molecules may represent a promising therapeutic strategy in TN-IBC patients