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ID 117318
Title Alternative
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
Author
Chen, Shuhai Tokushima University
Yamada, Shinichiro Tokushima University
Wada, Yuma Tokushima University
Keywords
cancer‑associated fibroblasts
epigallocatechin‑3‑gallate
aerobic glycolysis
reverse Warburg effect
colorectal cancer
Content Type
Thesis or Dissertation
Description
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.
Journal Title
International Journal of Oncology
ISSN
10196439
17912423
NCID
AA10992511
Publisher
Spandidos Publications
Volume
60
Issue
2
Start Page
19
Published Date
2022-01-14
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3743号
Diploma Number
甲医第1579号
Granted Date
2023-07-27
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital