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eSymposia | Myeloid Cells and Innate Immunity in Solid Tumors


Macrophage-dependent regulation of breast cancer iron homeostasis


Sep 21, 2020 12:00am ‐ Sep 21, 2020 12:00am

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Macrophage-dependent regulation of breast cancer iron homeostasis Daniel Greiner and Minna Roh-Johnson Triple negative breast cancer (TNBC) cells have high metabolic requirements, particularly for metabolites that drive redox reactions such as iron. Iron is so critical to cellular growth that sequestering iron away from a tumor can reduce numerous tumor proliferation in vitro. Despite these findings, pharmacological efforts to chelate iron and inhibit tumor progression in vivo have remained unsuccessful. To improve these efforts, we seek to understand how the microenvironment affects tumor iron homeostasis. Tumors acquire the majority of their iron from macrophages in the tumor microenvironment; Macrophages store high amounts of iron and can secrete iron in the presence of a tumor. In addition to iron secretion, macrophages can also promote tumor growth and cancer progression through both secreted signals and contact-mediated mechanisms. We will determine whether macrophage-tumor paracrine signaling can disrupt tumor iron homeostasis, affecting metastasis. Furthermore, we have identified that macrophages can transfer cytoplasm to cancer cells during metastasis. Thus, we will test whether macrophages make iron available to tumor cells through contact-mediated mechanisms, independent of secreted iron. To address these questions, we use primary human blood monocyte derived macrophages and TNBC cells in coculture to identify how changes occur in tumor iron homeostasis. Our preliminary data suggest macrophages may cause changes to the amount of available iron to the tumor, driving changes to tumor iron import and export. Furthermore, our data reveal a novel form of regulation in which macrophages may disrupt tumor iron homeostasis through direct transfer of iron or iron-associated proteins. Taken together, our findings suggest that macrophages promote iron dysregulation during tumor progression. Our future efforts will focus on determining the signaling mechanisms behind these changes, in an effort to identify potential drug targets that will prevent macrophage-dependent changes to tumor iron homeostasis.

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