Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression

• Material Type: 博士論文
• Title: Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression
• Author/Editor: Takehara, Masanori; Sato, Yasushi; Kimura, Tetsuo; Noda, Kazuyoshi; Miyamoto, Hiroshi; Fujino, Yasuteru; Miyoshi, Jinsei; Nakamura, Fumika; Wada, Hironori; Bando, Yoshimi; Ikemoto, Tetsuya; Shimada, Mitsuo; Muguruma, Naoki; Takayama, Tetsuji
• Author Heading: Takehara, Masanori; Sato, Yasushi; Kimura, Tetsuo; Noda, Kazuyoshi; Miyamoto, Hiroshi; Fujino, Yasuteru; Miyoshi, Jinsei; Nakamura, Fumika; Wada, Hironori; Bando, Yoshimi; Ikemoto, Tetsuya; Shimada, Mitsuo; Muguruma, Naoki; Takayama, Tetsuji
• Publication, Distribution, etc.: Japanese Cancer Association|John Wiley & Sons
• Publication Date: 2020-06-14
• Publication Date (W3CDTF): 2020-06-14
• Alternative Title: 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
• Periodical title: Cancer Science
• No. or year of volume/issue: 111 8
• Volume: 111
• Issue: 8
• Pages: 2883-2894
• ISSN (Periodical Title): ISSN : 1349-7006
• Degree grantor/type: 徳島大学
• Date Granted: 2020-09-24
• Dissertation Number: 甲第3459号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: pancreatic cancer; cancer-associated adipocytes; SAA1; metastasis; EMT; cancer microenvironment
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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.
• Related Material (DOI): 10.1111/cas.14527
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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