| Item type |
文献 / Documents(1) |
| 公開日 |
2020-10-13 |
| アクセス権 |
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|
アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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|
関連識別子 |
https://doi.org/10.1111/cas.14527 |
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関連名称 |
10.1111/cas.14527 |
| 出版タイプ |
|
|
出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression |
| タイトル別表記 |
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その他のタイトル |
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
佐藤, 康史
木村, 哲夫
野田, 和克
宮本, 弘志
藤野, 泰輝
三好, 人正
中村, 文香
ワダ, ヒロノリ
坂東, 良美
池本, 哲也
島田, 光生
六車, 直樹
高山, 哲治
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| 抄録 |
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内容記述 |
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. |
| キーワード |
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主題 |
pancreatic cancer |
| キーワード |
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|
主題 |
cancer-associated adipocytes |
| キーワード |
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|
主題 |
SAA1 |
| キーワード |
|
|
主題 |
metastasis |
| キーワード |
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|
主題 |
EMT |
| キーワード |
|
|
主題 |
cancer microenvironment |
| 書誌情報 |
en : Cancer Science
巻 111,
号 8,
p. 2883-2894,
発行日 2020-06-14
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
13497006 |
| 出版者 |
|
|
出版者 |
Japanese Cancer Association |
| 出版者 |
|
|
出版者 |
John Wiley & Sons |
| 備考 |
|
|
値 |
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。
学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻） |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, 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. |
| EID |
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識別子 |
366787 |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3459号 |
| 学位記番号 |
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|
値 |
甲医第1466号 |
| 学位授与年月日 |
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|
学位授与年月日 |
2020-09-24 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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|
学位授与機関名 |
徳島大学 |
k3459_abstract_review.pdf (212 KB)
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