Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression

• Material Type: 博士論文
• ISSN: 1349-7006
• Title: Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression
• Volume: 111 8
• 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
• Degree grantor/type: 徳島大学
• Date Granted: 2020-09-24
• Date Granted (W3CDTF): 2020-09-24
• Dissertation Number: 甲第3459号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3459号
• 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.
• DOI: info:doi/10.1111/cas.14527; https://doi.org/info:doi/10.1111/cas.14527
• Persistent ID (NDL): info:ndljp/pid/11570280; https://dl.ndl.go.jp/pid/11570280
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-11-10T19:58:22+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/115328
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp