A study on the role of cytokines in modulating proteolytic activity and associated signaling pathways in breast cancer progression / Eslam Ahmed Elghonaimy ; Supervised Tahani Elmamlouk , Mona Mostafa Mohamed , Mohamed Elsayed Elshinawi

Thesis (Ph.D.) - Cairo University - Faculty of Science - Department of Zoology

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer especially with triple negative (TN) IBC patients where they cannot be treated with endocrine therapy or targeted therapy. Despite the fact that there is a growing literature describing the role of macrophages in breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is yet unclear. The aim of the present study was to isolate and characterize tumor associated macrophages of IBC and non-IBC patients and de{uFB01}ne their role in tumor progression and metastasis. It was found that macrophages highly in{uFB01}ltrated into carcinoma tissues of IBC patients. In addition, cytokine pro{uFB01}ling of CD14+ cells isolated from IBC patients revealed a signi{uFB01}cant increase in secretion of TNF-Ü, MCP-1/CCL2, IL-8 and IL-10 as compared to CD14+ cells isolated from non-IBC patients. TNF-Ü, IL-8 and IL-10 signi{uFB01}cantly increased motility and invasion of IBC cells in vitro. On the other hand, cathepsin B expression and Src-Erk1/2 pathway were significantly increased in IBC-TN carcinoma tissues as compared to non- IBC-TN patients. Moreover, MCP-1/CCL2 and IL-8 stimulated proteolytic activity, cathepsin B expression and Src-ERK1/2 pathway in TNBC cell lines SUM149 and HCC70. Targeting MCP-1/CCL2, IL-8 and their associated signaling pathway axis Src-Erk1/2 in triple negative IBC patients represents a promising therapeutic strategy in treatment of those patients

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