Downregulation of 15‐hydroxyprostaglandin dehydrogenase by interleukin‐1β from activated macrophages leads to poor prognosis in pancreatic cancer

Arima, Kei; Komohara, Yoshihiro; Bu, Luke; Tsukamoto, M; Itoyama, Rumi; Miyake, Keisuke; Uchihara, Tomoyuki; Ogata, Yoko; Nakagawa, Shigeki; Okabe, Hidetoshi; Imai, Katsunori; Hashimoto, Daisuke; Chikamoto, Akira; Yamashita, Yo‐ichi; Baba, Hideo; Ishimoto, Takatsugu

doi:10.1111/cas.13467

Cited by 37 publications

(40 citation statements)

References 32 publications

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“…IL-1β derived from TAMs suppresses the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme involved in prostaglandin degradation in PDAC cells, which results in tumor growth and poor prognosis for PDAC patients [ 145 ]. It can also increase COX-2 expression in human breast cancer cells, thus contributing to cancer progression [ 146 ].…”

Section: Pro-and Anti-tumor Effects Of Il-1βmentioning

confidence: 99%

Interleukin-1β and Cancer

Rébé

Ghiringhelli

2020

Cancers

216

110

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Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment.

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Section: Pro-and Anti-tumor Effects Of Il-1βmentioning

confidence: 99%

Interleukin-1β and Cancer

Rébé

Ghiringhelli

2020

Cancers

216

110

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“…A number of studies have shown that inflammation triggered infiltration of immune cells in the PAAD microenvironment was closely associated with pancreatic cancer cells growth, metastasis and poor clinical outcomes. [ 24 , 28 , 29 ] In this study, we found that a greater immune score was significantly correlated with advanced TNM stage (stage IIA, stage IIB, stage III, and stage IV) ( P = .0367), which indicate that interactions of the surrounding microenvironment play an important role in the development and progression of PAAD.…”

Section: Discussionmentioning

confidence: 61%

Relationship between a 7-mRNA signature of the pancreatic adenocarcinoma microenvironment and patient prognosis (a STROBE-compliant article)

Jiang²,

Zhang³

et al. 2020

Medicine

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The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes. The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database. A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group ( P < .0001, P = .0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part. A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.

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“…Furthermore, IL-1β facilitates cell migration by stimulating the synthesis of HIF-1α under non-hypoxic conditions (Filippi et al, 2015). It also causes angiogenesis by increasing CxCL8 / CXCR1 (Filippi et al, 2015), VEGF (Voronov et al, 2003), EGFR and IL-8 (Lee et al, 2015), as well as secondary tumorigenesis with a greater production of ROS, COX2, NADPH oxidase and reduction of 15-PGDH (Arima et al, 2017). Some authors attribute the rise in IL-1β plasma to an increased risk of cervical cancer in women with polymorphisms (Qian et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of IL-1β and IL-18 Proinflammatory Interleukins Increases the Risk of Developing Cervical Cancer

Matamoros

Silva

Moura

et al. 2019

Asian Pac J Cancer Prev

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Background: The objective of this study was to analyze the gene expression profile of the proinflammatory interleukins, (IL-1β and IL-18) in patients with premalignant lesions and cervical cancer. Methods: Total IL-1β and IL-18 mRNA was quantified by qPCR to obtain the expression data in cervical tissues. A total of 74 cervical biopsies were obtained from women undergoing a colposcopy. The samples were divided into: normal (19), low level lesions (LSIL) or NIC I (17), high level lesions (HSIL) or CIN II and CIN III (29) and cancer (9). The normal cervical tissue samples were included as controls. The OR and 95% CI were calculated for the determination of the risk of progression between each type of lesion and cancer using logistic regression. Results: The results showed that an increase in the risk of progression of pre-neoplastic lesions to cancer was between 2.5 and 2.08 times higher in women with lower IL-1β and IL-18 expression, respectively. Conclusions: This study provided evidence that IL-1β and IL-18 are potential biomarkers that can be explored in further studies for monitoring the evolution of pre-neoplastic lesions and avoiding overtreatment or undertreatment of the patients.

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Downregulation of 15‐hydroxyprostaglandin dehydrogenase by interleukin‐1β from activated macrophages leads to poor prognosis in pancreatic cancer

Cited by 37 publications

References 32 publications

Interleukin-1β and Cancer

Interleukin-1β and Cancer

Relationship between a 7-mRNA signature of the pancreatic adenocarcinoma microenvironment and patient prognosis (a STROBE-compliant article)

Reduced Expression of IL-1β and IL-18 Proinflammatory Interleukins Increases the Risk of Developing Cervical Cancer

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