S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Breast Cancer Cell-Derived Soluble CD44 Promotes Tumor Progression by Triggering Macrophage IL1 beta Production
- Jang, Jeong-Hoon; Kim, Do-Hee; Lim, Jae Min; Lee, JoonWon; Jeong, Su Jin; Kim, Kwang Pyo; Surh, Young-Joon
- Issue Date
- Cancer Research, Vol.80 No.6, pp.1342-1356
- IL1 beta is a central regulator of systemic inflammatory response in breast cancer, but the precise regulatory mechanisms that dictate the overproduction of IL1 beta are largely unsolved. Here, we show that IL1 beta secretion is increased by the coculture of human monocyte-like cells and triple-negative breast cancer (TNBC) cells. In addition, macrophages robustly produced IL1 beta when exposed to the conditioned media of TNBC cells. Consistent with these observations, macrophage depletion decreased serum IL1 beta and reduced breast cancer progression in an orthotopic breast cancer mouse model. Profiling the secretome of human breast cancer cells revealed that the CD44 antigen was the most differentially released protein in basal conditions of TNBC cells. Antibody-mediated neutralization of CD44 abrogated IL1 beta production in macrophages and inhibited the growth of primary tumors. These results suggest IL1 beta-mediated oncogenic signaling is triggered by breast cancer cell membrane-derived soluble CD44 (sCD44) antigen, and targeting sCD44 antigen may provide an alternative therapeutic strategy for breast cancer treatment by modulating inflammatory tumor microenvironment. Significance: A novel positive feedback loop between IL1 beta and CD44 promotes TNBC malignant progression.
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