論文 - 詳細
| RRC ID | 63785 |
|---|---|
| 著者 | Takehara M, Sato Y, Kimura T, Noda K, Miyamoto H, Fujino Y, Miyoshi J, Nakamura F, Wada H, Bando Y, Ikemoto T, Shimada M, Muguruma N, Takayama T. |
| タイトル | Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression. |
| ジャーナル | Cancer Sci |
| Abstract |
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. |
| 巻・号 | 111(8) |
| ページ | 2883-2894 |
| 公開日 | 2020-8-1 |
| DOI | 10.1111/cas.14527 |
| PMID | 32535957 |
| PMC | PMC7419047 |
| MeSH | 3T3 Cells Adipocytes / pathology* Adult Aged Aged, 80 and over Animals Cell Dedifferentiation Cell Line, Tumor Cell Proliferation Coculture Techniques Culture Media, Conditioned / metabolism Disease Progression Disease-Free Survival Epithelial-Mesenchymal Transition Female Follow-Up Studies Gene Knockdown Techniques Humans Male Mice Middle Aged Pancreas / pathology Pancreas / surgery Pancreatectomy Pancreatic Neoplasms / mortality Pancreatic Neoplasms / pathology* Pancreatic Neoplasms / surgery Prognosis RNA, Small Interfering / metabolism Retrospective Studies Serum Amyloid A Protein / genetics Serum Amyloid A Protein / metabolism* |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PK-1(RCB1972) PK-45H(RCB1973) PK-8(RCB2700) |