論文 - 詳細
| RRC ID | 72020 |
|---|---|
| 著者 | Jinno N, Yoshida M, Hayashi K, Naitoh I, Hori Y, Natsume M, Kato A, Kachi K, Asano G, Atsuta N, Sahashi H, Kataoka H. |
| タイトル | Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer. |
| ジャーナル | Cancer Sci |
| Abstract |
Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX-LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. In a PDAC peritoneal dissemination mouse model, the amount of ATX was significantly higher in ascites than in serum. An in vitro study using two PDAC cell lines, AsPC-1 and PANC-1, showed that ATX-LPA signaling promoted cancer cell migration via the activation of the downstream signaling, and this increased cell migration was suppressed by an ATX inhibitor, PF-8380. An in vivo study showed that PF-8380 suppressed peritoneal dissemination and decreased malignant ascites, and these results were validated by the biological analysis as well as the in vitro study. Moreover, there was a positive correlation between the amount of ATX in ascites and the degree of disseminated cancer progression. These findings demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC. |
| 巻・号 | 112(2) |
| ページ | 668-678 |
| 公開日 | 2021-2-1 |
| DOI | 10.1111/cas.14689 |
| PMID | 33053268 |
| PMC | PMC7893983 |
| MeSH | Animals Ascites / metabolism Ascites / pathology Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / secondary* Female Heterografts Humans Mice Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness / pathology Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Peritoneal Neoplasms / metabolism Peritoneal Neoplasms / secondary* Phosphoric Diester Hydrolases / 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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 | PANC-1(RCB2095) |