直近一年間の累計
アクセス数 : ?
ダウンロード数 : ?
ID 117318
タイトル別表記
EGCG HINDERS METABOLIC COUPLING BETWEEN CANCER AND CAFs
エピガロカテキン-3-ガレートはがん関連線維芽細胞における糖代謝制御することで、metabolic couplingを阻害し、大腸癌細胞の腫瘍悪性度を抑制する
著者
陈, 述海 徳島大学大学院医学研究科(医学専攻)
Yamada, Shinichiro Tokushima University
Wada, Yuma Tokushima University
キーワード
cancer‑associated fibroblasts
epigallocatechin‑3‑gallate
aerobic glycolysis
reverse Warburg effect
colorectal cancer
資料タイプ
学位論文
抄録
In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancer‑associated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin‑3‑gallate (EGCG) exerts anti‑tumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through co‑culture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells in vitro. EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumor‑promoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumor‑promoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of anti‑cancer therapy.
掲載誌名
International Journal of Oncology
ISSN
10196439
17912423
cat書誌ID
AA10992511
出版者
Spandidos Publications
60
2
開始ページ
19
発行日
2022-01-14
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Shuhai Chenの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3743号
学位記番号
甲医第1579号
学位授与年月日
2023-07-27
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院