Inflammasome-driven IL-1ß and IL-18 cytokine signaling between macrophages and cancer cells within the breast tumor microenvironment
1 online resource (45 pages) : PDF
University of North Carolina at Charlotte
Breast cancer especially triple-negative breast cancer remains deadly, despite detection, monitoring and therapeutic advances. Indeed, aggressive breast cancers metastasize to tissues including the brain, bones, and lungs. Metastasis is favored by a pro-inflammatory tumor microenvironment regulated in part by tumor-associated macrophages. Macrophages especially secrete the pro-inflammatory cytokines IL-1ß and IL-18 mainly following the activation of inflammasomes. The role of the inflammasome-driven pro-inflammatory IL-1ß and IL-18 cytokines in the cross-talk between macrophages and tumor cells within the breast tumor microenvironment remains to be elucidated. Here, we used in vitro models to assess the role of inflammasome in the production of IL-1ß, IL-18 and the subsequent effects of IL-1ß and IL-18 on both 4T1 mammary tumor growth and J774, RAW and bone marrow derived macrophages. Our in vitro results demonstrate that (1) inflammasome proteins are expressed and co-localized in 4T1 tumor cells and in J774 macrophages; (2) conditioned media from inflammasome-activated 4T1 cells promoted macrophage secretions of inflammasome-related cytokines, (3) conditioned media from inflammasome-activated macrophages promoted 4T1 cell growth. Furthermore, (4) recombinant IL-18 reduced J774 cell growth and, dose-dependently, 4T1 cell growth. Finally, IL-18BP abrogated IL-18-driven J774 growth inhibition. Taken together, these data suggest that inflammasome modulation, especially through the disruption of the IL-18/IL-18BP signaling, may have potential therapeutic benefit for breast cancer patients.
Reitzel, AdamTruman, Andrew
Thesis (M.S.)--University of North Carolina at Charlotte, 2018.
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). For additional information, see http://rightsstatements.org/page/InC/1.0/.
Copyright is held by the author unless otherwise indicated.