| 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
|
| リソース情報 |
| ヒト・動物細胞 |
PANC-1(RCB2095) |
