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
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著者 |
野田, 和克
Tokushima University
三好, 人正
Tokushima University
中村, 文香
Tokushima University
Wada, Hironori
Tokushima University
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キーワード | pancreatic cancer
cancer-associated adipocytes
SAA1
metastasis
EMT
cancer microenvironment
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資料タイプ |
学位論文
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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.
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掲載誌名 |
Cancer Science
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ISSN | 13497006
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出版者 | Japanese Cancer Association|John Wiley & Sons
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巻 | 111
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号 | 8
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開始ページ | 2883
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終了ページ | 2894
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発行日 | 2020-06-14
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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 | |
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フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3459号
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学位記番号 | 甲医第1466号
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学位授与年月日 | 2020-09-24
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
医学系
病院
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