S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Theses (Master's Degree_분자의학 및 바이오제약학과)
Anti-tumorigenic Activity of Human Cysteinyl-tRNA Synthetase via Immune Stimulation
면역 촉진을 통한 Human Cysteinyl-tRNA Synthetase의 항암 활성
- 융합과학기술대학원 분자의학 및 바이오제약학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과, 2018. 2. 김성훈.
- Cancer immunotherapy drug is getting the spotlight in cancer therapy field as a new method for treating patients in cancer. Its supportive role in immune system covers disadvantages from conventional treatments (chemotherapy, surgical resection and radiotherapy) by lowering toxicity, encouraging durability, and extending applicable types and stages of tumor. Here, we used aminoacyl-tRNA synthetases (ARSs), which are commonly known for ligating amino acids to their cognate tRNAs, as a new candidate for cancer immunotherapy. Even though its role as a housekeeping enzyme has been known, evidence on non-canonical function of ARSs is mounting and its involvement in human diseases has been discovered. We proved that cysteinyl-tRNA synthetase (CRS) has an ability to suppress tumor growth by stimulating immune responses. Through the screening using syngeneic mouse model, we confirmed that CRS could suppress the tumor growth. With the binding assay using different cell types, we observed that recombinant CRS bound specifically to the macrophage and induced migration and TNF-α secretion of RAW 264.7 cells in vitro. In addition, CRS showed antitumorigenic activity by inducing TNF-α secretion and infiltration of macrophages into the tumor microenvironment in vivo. Lastly, we used various cytokines and growth factors to figure out physiological condition of CRS secretion. Interestingly, CRS was secreted from colon cancer cell line in response to TNF-α and tunicamycin (ER stress). Through this work, we concluded that secreted CRS might act as a chemokine or pro-inflammatory cytokine to stimulate immune response, thereby leading to anti-tumor response.