Relationship between blood plasma prostaglandin E2 and liver and lung metastases in colorectal cancer

Narisawa, Tomio; Kusaka, Hisashi; Yamazaki, Yoshihiko; Takahashi, Masahiro; Koyama, H; Koyama, Kenji; Fukaura, Yoko; Wakizaka, Akira

doi:10.1007/bf02051919

Cited by 56 publications

(13 citation statements)

References 15 publications

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“…38 Levels of PGE 2 and Tregs in the peripheral blood also may reflect the biology of the disease and motivate the use of an anti-COX-2 and anti-Treg therapy. 39,40 To develop novel therapeutic strategies, we must gain insight into the mechanisms of Treg control and regulation in UM.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Mougiakakos

Johansson

Trocmé

et al. 2010

Cancer

115

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BACKGROUND: Forkhead box P3 (FOXP3)-positive regulatory T cells (Tregs) are key mediators of peripheral tolerance and suppress efficient antitumor responses. Prostaglandin E 2 (PGE 2 ) produced by inducible cyclooxygenase-2 (COX-2) can lead to Treg induction. COX-2 expression has been linked to tumorigenesis and growth in various malignancies. The objective of the current study was to investigate whether Tregs infiltrate uveal melanomas (UMs) and whether their prevalence is linked to COX-2 expression and the prediction of overall survival (OS). METHODS: One hundred patients who underwent enucleation after they were diagnosed with UM were included in the study. Immunohistochemical staining with monoclonal anti-FOXP3, anti-CD4, and anti-COX-2 antibodies was performed, and immunoreactivity was assessed. Correlations of COX-2 expression with the presence of Tregs, established clinicopathologic parameters, and OS were evaluated in univariate and multivariate analyses. RESULTS: High expression of COX-2 was predictive of shortened OS. FOXP3-positive Tregs were detectable in 24% of UMs and were restricted to malignant tissue. The extent of COX-2 expression was associated significantly with Treg prevalence (P ¼ .004) and Treg intratumoral localization (P ¼ .005). Intratumoral Tregs (but not the prevalence of Tregs) were independent marker for worse OS with a hazard ratio of 5.36 in patients with COX-2-positive tumors. CONCLUSIONS:The current results demonstrated that high COX-2 expression is associated with OS and Treg prevalence in UM. These findings are in line with the observations that COX-2/PGE 2 induces Tregs and that Tregs may alter antitumor responses, resulting in a negative effect on the clinical disease course. Intratumoral Tregs are an independent prognostic marker for COX

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Section: Discussionmentioning

confidence: 99%

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Mougiakakos

Johansson

Trocmé

et al. 2010

Cancer

115

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“…[25][26][27] It has been reported that there was a correlation between an increased PGE 2 concentration and the risk of cancer development. [28][29][30][31] On the other hand, PGE 1 converted from DGLA has anti-inflammatory [32][33][34] and anti-platelet aggregation activities. 4) It has been indicated that DGLA and PGE 1 inhibited the synthesis of pro-inflammatory mediators such as LTB 4 , LTC 4 , and LTD 4 .…”

Section: Discussionmentioning

confidence: 99%

Distribution and Metabolism of Dihomo-γ-linolenic Acid (DGLA, 20:3n-6) by Oral Supplementation in Rats

Umeda-Sawada

Fujiwara

Ushiyama

et al. 2006

Bioscience, Biotechnology, and Biochemistry

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We compared the dietary effects of dihomo-gamma-linolenic acid (DGLA) contained in the DGLA oil produced by a fungus with gamma-linolenic acid (GLA) on the fatty acid composition. Wistar rats were fed with three kinds of oil for two weeks as follows: (i) control group: corn oil; (ii) GLA group: borage oil; (iii) DGLA group: DGLA oil/safflower oil = 55:45. The DGLA concentrations in the liver, serum, and brain of the DGLA group were higher than those of the GLA oil group. We also examined the dose effect of DGLA. The DGLA levels in the liver, serum, and brain significantly increased with increasing dosage of DGLA in the diet. DGLA administration significantly increased the ratio of PGE1/PGE2 in the rat plasma. The mechanism for GLA administration to improve atopic eczema is thought to involve an increase in the concentration of DGLA metabolized from GLA, so these results suggest that the dietary effect of DGLA would be more dominant than GLA.

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“…Although NSAIDs inhibit cyclooxygenase which catalyses the biosynthesis of PGH 2 , precursors for prostanoids such as prostaglandins, the mechanisms by which inhibition of PG synthesis contribute to decreased carcinogenesis in colon and some other tissues have yet to be defined. In addition to breast cancer, studies have shown that colon cancer tissues produce a large amount of PGE 2 (Narisawa et al, 1990). Moreover, our very recent study showed that a potent stimulatory effect of IL-1 on HGF production in fibroblasts was mediated via PGE 2 production and was almost completely abrogated by indomethacin (unpublished data).…”

Section: Discussionmentioning

confidence: 73%

Prostaglandin production in mouse mammary tumour cells confers invasive growth potential by inducing hepatocyte growth factor in stromal fibroblasts

1999

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SummaryInteractions between stromal and mammary tumour cells play a crucial role in determining the malignant behaviour of tumour cells. Although MMT mouse mammary tumour cells do not produce hepatocyte growth factor (HGF), addition of conditioned medium (CM) from MMT cells to cultures of human fibroblasts derived from skin and breast tissues stimulated the production of HGF, thereby indicating that MMT cells secrete an inducing factor for HGF. This HGF-inducing factor, purified from MMT-derived CM, proved to be prostaglandin E 2 (PGE 2 ). Consistently, treatment of MMT cells with indomethacin, an inhibitor of cyclooxygenase, abolished this HGF-inducing activity in MMT-derived CM, while treatment of MMT cells with HGF stimulated cell growth and cell motility. Likewise, HGF strongly enhanced urokinase-type plasminogen activator activity and invasion of MMT cells through Matrigel: a 15-fold stimulation in the invasion of MMT cells was seen by HGF. Finally, MMT cells in the upper compartment were co-cultivated with fibroblasts in the lower compartment of the Matrigel chamber, HGF levels in the co-culture system exceeded the level in fibroblasts alone and suppression occurred with exposure to indomethacin. Together with increase in the HGF level, the invasion of MMT cells was enhanced by co-cultivation with fibroblasts, whereas the increased invasion of MMT cells was significantly inhibited by an anti-HGF antibody and by indomethacin. These results indicate mutual interactions between MMT cells and fibroblasts: MMT-derived PGE 2 plays a role in up-regulating HGF production in fibroblasts, while fibroblast-derived HGF leads to invasive growth in MMT cells. The mutual interactions mediated by HGF and prostaglandins may possibly be a mechanism regulating malignant behaviour of mammary tumour cells, through tumour-stromal interactions.

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Relationship between blood plasma prostaglandin E2 and liver and lung metastases in colorectal cancer

Cited by 56 publications

References 15 publications

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Distribution and Metabolism of Dihomo-γ-linolenic Acid (DGLA, 20:3n-6) by Oral Supplementation in Rats

Prostaglandin production in mouse mammary tumour cells confers invasive growth potential by inducing hepatocyte growth factor in stromal fibroblasts

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