Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1β from activated macrophages leads to poor prognosis in pancreatic cancer.
Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1β from activated macrophages leads to poor prognosis in pancreatic cancer.
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DOI：
10.1111/cas.13467
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发表时间：
2018-03
期刊：
影响因子：
5.7
通讯作者：
Ishimoto T
中科院分区：
文献类型：
--
作者：
Arima K;Komohara Y;Bu L;Tsukamoto M;Itoyama R;Miyake K;Uchihara T;Ogata Y;Nakagawa S;Okabe H;Imai K;Hashimoto D;Chikamoto A;Yamashita YI;Baba H;Ishimoto T
慢性炎症在癌症发生和各种肿瘤（包括胰腺导管腺癌（PDAC））的进展中起着至关重要的作用。花生四烯酸级联是产生多种代谢物（例如前列腺素 E2）的主要炎症途径。 15-羟基前列腺素脱氢酶 (15-PGDH) 可降解前列腺素，并且在多种类型的癌症中其含量经常降低；然而，15-PGDH抑制的分子机制尚不清楚。本研究旨在阐明 PDAC 中 15-PGDH 抑制的分子机制和临床意义。在这里，我们发现白介素-1β（IL-1β）是一种促炎细胞因子，下调 PDAC 细胞中 15-PGDH 的表达，并且 IL-1β 表达与冷冻 PDAC 组织中的 15-PGDH 水平呈负相关。我们还发现激活的巨噬细胞产生 IL-1β 并减少 PDAC 细胞中 15-PGDH 的表达。此外，通过对 107 个 PDAC 样本进行免疫组织化学染色，发现 CD163 阳性肿瘤相关巨噬细胞的数量与 PDAC 细胞中的 15-PGDH 水平呈负相关。最后，我们发现15-PGDH低表达与PDAC患者的晚期肿瘤、淋巴结转移和神经侵犯以及不良预后显着相关。我们的结果表明，TAM 衍生的 IL-1β 抑制 PDAC 细胞中 15-PGDH 的表达，导致 PDAC 患者预后不良。
Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2. The enzyme 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15‐PGDH suppression are unclear. The current study was carried out to elucidate the molecular mechanisms and clinical significance of 15‐PGDH suppression in PDAC. Here, we showed that interleukin‐1β (IL‐1β), a pro‐inflammatory cytokine, downregulates 15‐PGDH expression in PDAC cells, and that IL‐1β expression was inversely correlated with 15‐PGDH levels in frozen PDAC tissues. We also found that activated macrophages produced IL‐1β and reduced 15‐PGDH expression in PDAC cells. Furthermore, the number of CD163‐positive tumor‐associated macrophages was shown to be inversely correlated with 15‐PGDH levels in PDAC cells by immunohistochemical staining of 107 PDAC samples. Finally, we found that low 15‐PGDH expression was significantly associated with advanced tumors, presence of lymph node metastasis and nerve invasion, and poor prognosis in PDAC patients. Our results indicate that IL‐1β derived from TAMs suppresses 15‐PGDH expression in PDAC cells, resulting in poor prognosis of PDAC patients.
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影响因子：
3.7
作者：
Sugihara H;Ishimoto T;Watanabe M;Sawayama H;Iwatsuki M;Baba Y;Komohara Y;Takeya M;Baba H
通讯作者：
Baba H
DOI：
10.1152/ajpgi.00348.2005
发表时间：
2006-02-01
影响因子：
4.5
作者：
Otani, T;Yamaguchi, K;Dannenberg, AJ
通讯作者：
Dannenberg, AJ
影响因子：
9
作者：
Neoptolemos, JP;Stocken, DD;Büchler, MW
通讯作者：
Büchler, MW
影响因子：
168.9
作者：
Rothwell, Peter M.;Fowkes, F. Gerald R.;Meade, Tom W.
通讯作者：
Meade, Tom W.
影响因子：
11.2
作者：
Wolf, Ido;O'Kelly, James;Koeffler, H. Phillip
通讯作者：
Koeffler, H. Phillip