S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Cancer Biology (협동과정-종양생물학전공) Theses (Master's Degree_협동과정-종양생물학전공)
A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model
마우스 골수기원억제세포와 유방암 세포간의 IL-6 트랜스 신호전달 상호활성화고리를 통한 자발적인 전이촉진에 관한 연구
- 의과대학 협동과정 종양생물학전공
- Issue Date
- 서울대학교 대학원
- Myeloid-derived suppressor cells (MDSCs); Breast cancer cells; IL-6 trans-signaling; Tumor metastasis
- 학위논문 (석사)-- 서울대학교 대학원 : 협동과정 종양생물학 전공, 2013. 2. 이동섭.
- Tumor cell interactions with the microenvironment, especially those of bone-marrow-derived myeloid cells, are important in various aspects of tumor metastasis. Myeloid-derived suppressor cells (MDSCs) have been suggested to constitute tumor-favoring microenvironments. I evaluated whether MDSCs potentiated by cancer cells directly increased breast cancer aggressiveness, leading to spontaneous distant metastasis of cancer cells.Usingamurine breast cancer cell model, I showed that murine breast cancer cells with high IL-6 expression recruited more MDSCs, and that the metastasizing capacity of cancer cells paralleled MDSC recruitment in tumor-bearing mice. Metastasizing, but not non-metastasizing, tumor-derived factors induced MDSCs to increase IL-6 production and full activation of recruited MDSCs occurred in the primary tumor site and metastatic organ in the vicinity of metastasizing cancer cells, but not in lymphoid organs. In addition, tumor-expanded MDSCs expressed Adam-family proteases, which facilitated shedding of IL-6 receptor, thereby contributing to breast cancer cell invasiveness and distant metastasis through IL-6 trans-signaling. The critical role of IL-6 trans-signaling was confirmed in both the afferent and efferent pathways of metastasis. Collectively, my findings reveal that breast cancer cells and MDSCs form a synergistic mutual feedback loop and that thus-potentiated MDSCs directly affect breast cancer cell aggressiveness, leading to spontaneous metastasis.