Role of Protein Disulfide Isomerase, CPR-1, in Tumor Development in Different Tumor-bearing Mice

• Main Authors: Tzung-Yan Chen, 陳宗彥
• Other Authors: Wen-Chen Yang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/13933186423355232972

碩士 === 國立陽明大學 === 藥理學研究所 === 101 === Protein disulfide isomerase (PDI) family can catalyze the formation of disulfide bond and, in turn, protein folding. PDIs have one to three thioredoxin homology domains containing the Cys-Gly-His-Cys motif. Apart from the protein folding activity, PDIs also have non-Endoplasmic Reticulum functions. CPR-1, a PDI member, was identified as one of the cytopiloyne-bond protein. However, little is known about the function of CPR-1 in tumor development. To study the role of CPR-1 in tumor development, CPR-1- knockdown tumor cell lines and CPR-1-deficient mice were generated in our laboratory. We discovered that cell doubling time was increased when cell CPR-1 knockdown. In tumor-bearing mice, we found that tumor development in WT mice was faster than CPR-1 KO mice as evidenced by tumor volume and weight. Consistently, CPR-1 KO tumor-bearing mice survived longer than WT tumor-bearing mice. Moreover, the metastasis lung nodules in CPR-1 KO mice were decreased in comparison with WT mice. In order to further investigate the impact of CPR-1 knockout in tumor microenvironment, we isolated bone marrow cells, splenocytes and tumor infiltrating leukocytes to analyze the cell proportion and cell number. Meanwhile, we purified myeloid-derived suppressor cells (MDSC) to carry out functional assay. Results showed that MDSC from CPR-1 KO tumor-bearing mice were relatively ineffective in T effector proliferation suppression and regulatory T cell induction, which compared to MDSC from WT tumor-bearing mice which can suppress immune response from host immune system, resulting in different tumor development. In conclusion, CPR-1 in tumor cells and microenvironment is required for tumor growth and metastasis.