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ID 115328
タイトル別表記
癌関連脂肪細胞は膵癌のSAA1発現を誘導して膵癌の進展を促進する
著者
武原, 正典 徳島大学大学院医科学教育部(医学専攻) KAKEN研究者をさがす
木村, 哲夫 Tokushima University|Clinic Green House KAKEN研究者をさがす
野田, 和克 Tokushima University
三好, 人正 Tokushima University
Wada, Hironori Tokushima University
キーワード
pancreatic cancer
cancer-associated adipocytes
SAA1
metastasis
EMT
cancer microenvironment
資料タイプ
学位論文
抄録
Although pancreatic cancer often invades peripancreatic adipose tissue, little information is known about cancer-adipocyte interaction. We first investigated the ability of adipocytes to de-differentiate to cancer-associated adipocytes (CAAs) by co-culturing with pancreatic cancer cells. We then examined the effects of CAA-conditioned medium (CAA-CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3-L1 adipocytes were co-cultured with pancreatic cancer cells (PANC-1) using the Transwell system, adipocytes lost their lipid droplets and changed morphologically to fibroblast-like cells (CAA). Adipocyte-specific marker mRNA levels significantly decreased but those of fibroblast-specific markers appeared, characteristic findings of CAA, as revealed by real-time PCR. When PANC-1 cells were cultured with CAA-CM, significantly higher migration/invasion capability, chemoresistance, and epithelial-mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC-1 cells cultured with CAA-CM and found a 78.5- fold higher expression of SAA1 compared with control cells. When the SAA1 gene in PANC-1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1-positive group was significantly shorter than in the SAA1-negative group (P = .013). In conclusion, we demonstrated that pancreatic cancer cells induced de-differentiation in adipocytes toward CAA, and that CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.
掲載誌名
Cancer Science
ISSN
13497006
出版者
Japanese Cancer Association|John Wiley & Sons
111
8
開始ページ
2883
終了ページ
2894
発行日
2020-06-14
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Masanori Takehara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 is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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3459号
学位記番号
甲医第1466号
学位授与年月日
2020-09-24
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院