研究拔尖：探討CEBPD在癌邊微環境功能及開發PTX3抑制劑以減緩癌症轉移與復發之轉譯應用

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(1)國立成功大學�邁向頂尖大學計畫 ˇ ˇ 延攬優秀人才工作報告表 NCKU’s “Aim for the Top University Project” Work Report Form for Distinguished Scholars. 續聘 continuation of employment ﹍離職 resignation 100 年 7 月 13 日更新受聘者姓名 Name of the Employee. 陳怡婷. 女. 男 Male. Female. 聘. 研究或教學或科技研發與研究拔尖「探討 CEBPD 在癌邊微環管理計畫名稱境功能及開發 PTX3 抑制劑以減緩 The project title of research, 癌症轉移與復發之轉譯應用 teaching, technology development and management. 補助延聘編號 Grant Number. 期. from. Period of to Employment. 104 年(y) 4 月(m) 1 日(d) 104 年(y) 7 月(m) 31 日(d). 計畫主持人 �申請單位主管王育民 Project Investigator (Head of Department/Center). 生物資訊與訊息傳遞研究所. HUA104-3-9-149. 一︾研究︾教學︾科技研發與管理工作全程經過概述〈�由受聘人填寫 Please summarize the entire research, teaching, or science and technology R&D and management work process completed by the employee). (To be. The previous study in this lab, in vitro and in vivo results show that CCAAT/enhancer binding protein delta (CEBPD), as a tumor suppressor, contributed to induce apoptosis and growth arrest. However, anti-cancer drugs not only activated CEBPD in cancer cells but also in tumor surrounding cells. I participated in investigating the potential of CEBPD suppression in tumor microenvironments to restrict tumor metastasis. I contributed significantly to the present grant to accomplish the works listed below. 1) CEBPD was induced by various inflammatory factors. Previous study demonstrated that M2 macrophages participated in tumor progression in response to inflammatory factors (1). We evaluated CEBPD expression in THP-1 cells, which is a human monocytic leukemia cell line and can be polarized into M2-like macrophage cells using a phorbol 12-myristate 13-acetate (2), after TNFα, PGE2 or IL-1β stimulations. The results showed that mRNA and protein levels of CEBPD were induced in human THP-1 cells and mouse M2 macrophages upon stimulations of TNFα, PGE2 or IL-1β (Figure 1).. Figure 1. The mRNA and protein levels of CEBPD were induced by TNFα, PGE2 and IL-1β in human THP-1 cells and mouse M2 macrophage cells. 1.

(2) 2) CEBPD involved in the regulation of migration and invasion of MDA-MB-231 cells. We further assessed whether CEBPD-expressing THP-1cells influence the migration and invasion capacities of cancer cells. The conditioned media from CEBPD-expressing THP-1 cells induced the migration and invasion of MDA-MB-231 cells (Figure 2 left). In contrast, the conditioned media from PGE2-treated THP-1 cells with lacking CEBPD significantly inhibited the migration and invasion of MDA-MB-231 cells (Figure 2 right). These results indicated that increased expression of CEBPD in THP-1 cells contributed to migration and invasion of MDA-MB-231 cells.. Figure 2. The migration and invasion capacities of MDA-MB-231 cells were assessed using a Boyden chamber assay. (Left) MDA-MB-231 cells were cultured in the conditioned medium from THP-1 cells that were transfected an empty vector (Ctl) or CEBPD expression vector (CD) using Lentivirus system. (Right) MDA-MB-231 cells were cultured in the conditioned medium from THP-1 cells, which were transfected with shLacZ (shC) or shCEBPD (shD) using Lentivirus system and then treated with or without PGE2. In the future, the role of CEBPD in M2 macrophages treated with the anticancer drugs, examples of cisplatin and 5-FU, will be assessed in vitro and in vivo. Reference 1. Italiani P, Boraschi D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Frontiers in immunology. 2014;5:514. 2. Daigneault M, Preston JA, Marriott HM, Whyte MK, Dockrell DH. The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PloS one. 2010;5:e8668.. 2.

(3) 二︾研究或教學或科技研發與管理成效評估�由計畫主持人或單位主管填寫 Please evaluate the performance of research, teaching or science and technology R&D and management Work: (To be completed by Project Investigator or Head of Department/Center). (1)是否達到延攬預期目標」 Has the expected goal of recruitment been achieved?. Dr. Chen, Yi-Ting participated in finding the roles of CEBPD in tumor surrounding cells to promote tumor metastasis and in investigating whether blockage of CEPBD in tumor microenvironment can reduce the ability of migration and invasion of cancer cells.. (2)研究或教學或科技研發與管理的方法︾專業知識及進度如何」 What are the methods, professional knowledge, and progress of the research, teaching, or R&D and management work?. Dr. Chen finished her PhD study in the Institute of Basic Medical Sciences in Nation Cheng-Kung University in 2014. She contributed significantly to this grant and helped to explore the roles of CEBPD in tumor microenvironment. Her progress matches the requirement and expectation.. (3)受延攬人之研究或教學或科技研發與管理成果對該計畫(或貴單位)助益如何」 How have the research, teaching, or R&D and management results of the employed person given benefit to the project (or your unit)?. Our college is well known for its research of basic and clinical medical science, fully equipped laboratories, animal facility, and library resource. Dr. Chen is eligible to use all these resources. With the help of Dr. Chen, we anticipate to facilitate publications of two more articles in significant SCI journals.. (4)受延攬人於補助期間對貴單位或國內相關學術科技領域助益如何」 How has the employed person, during his or her term of employment, benefited your unit or the relevant domestic academic field?. Actually, Dr. Chen is a well-trained scientist. Her expertise in glyco-science can help the development of medical science. In the future, after strengthening her training in my lab, Dr. Chen can apply the Research Assistant Professorship in any education and research institute.. (5)具體工作績效或研究或教學或科技研發與管理成果「 Please describe the specific work performance, or the results of research, teaching, or R&D and management work:. In addition to investigating the roles of CEBPD in tumor microenvironment, Dr. Chen also participates the study of hepatoma-derived growth factor in tumor microenvironment of pancreatic cancer. At present, she helps to finalize the project. Soon or later, one manuscript will be done before next February.. (6)是否續聘受聘人? Will you continue hiring the employed person? 續聘 Yes ﹍不續聘 No □ 此報告表篇幅以三ˇ四頁為原則〈This report form should be limited to 3-4 pages in principle. □ 此表格可上延攬優秀人才成果報告繳交說明網頁下載〈 This report form can be downloaded in http://scholar.lib.ncku.edu.tw/explain/ 3.

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