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Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity.

ABSTRACT: The involvement of inflammation in cancer progression has been the subject of research for many years. Inflammatory milieu and immune response are associated with cancer progression and recurrence. In different types of tumors, growth and metastatic phenotype characterized by the epithelial mesenchymal transition (EMT) process, stemness, and angiogenesis, are increasingly associated with intrinsic or extrinsic inflammation. Among the inflammatory mediators, prostaglandin E2 (PGE2) supports epithelial tumor aggressiveness by several mechanisms, including growth promotion, escape from apoptosis, transactivation of tyrosine kinase growth factor receptors, and induction of angiogenesis. Moreover, PGE2 is an important player in the tumor microenvironment, where it suppresses antitumor immunity and regulates tumor immune evasion, leading to increased tumoral progression. In this review, we describe the current knowledge on the pro-tumoral activity of PGE2 focusing on its role in cancer progression and in the regulation of the tumor microenvironment.

SUBMITTER: Finetti F

PROVIDER: S-EPMC7760298 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity.

Finetti Federica F Travelli Cristina C Ercoli Jasmine J Colombo Giorgia G Buoso Erica E Trabalzini Lorenza L

Biology 20201201 12

The involvement of inflammation in cancer progression has been the subject of research for many years. Inflammatory milieu and immune response are associated with cancer progression and recurrence. In different types of tumors, growth and metastatic phenotype characterized by the epithelial mesenchymal transition (EMT) process, stemness, and angiogenesis, are increasingly associated with intrinsic or extrinsic inflammation. Among the inflammatory mediators, prostaglandin E2 (PGE2) supports epith ...[more]

PMID: 33271839

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Project description:Eicosanoids, oxygenated metabolites of C20 polyunsaturated fatty acids (PUFAs), mediate fundamental physiological processes, including immune reactions and reproduction, in insects. Prostaglandins (PGs) make up one group of eicosanoids, of which PGE2 is a relatively well-known mediator in various insect taxa. While PG biosynthesis has been reported, the specific biosynthetic pathway for PGE2 is not known in insects. Here, we posed the hypothesis that Se-mPGES2 mediates biosynthesis of physiologically active PGE2 through its cognate protein. To test this hypothesis, we interrogated a transcriptome of the lepidopteran insect, Spodoptera exigua, to identify a candidate PGE2 synthase (Se-mPGES2) and analyzed its sequence and expression. Its predicted amino acid sequence contains a consensus thioredoxin homology sequence (Cys-x-x-Cys) responsible for catalytic activity along with an N-terminal membrane-associated hydrophobic domain and C-terminal cytosolic domain. It also shares sequence homology (36.5%) and shares almost overlapping three dimensional structures with a membrane-bound human PGES2 (mPGES2). Se-mPGES2 was expressed in all developmental stages with high peaks during the late larval instar and adult stages. Immune challenge significantly up-regulated its expression levels in hemocytes and fat body. Injecting double-stranded RNA (dsRNA) specific to Se-mPGES2 significantly impaired two cellular immune responses, hemocyte-spreading behavior and nodule formation following bacterial challenge. Humoral immunity was also significantly suppressed, registered as reduced phenoloxidase activity and antimicrobial peptide expression levels. The suppressed immune responses were reversed following PGE2, but not arachidonic acid (AA), treatments. RNAi treatments also reduced the egg-laying behavior of females. Control females mated with the RNAi-treated males led to substantially reduced egg-laying behavior, which was also reversed following PGE2 injections into females. These results strongly bolster our hypothesis that Se-mPGES2 acts in the biosynthesis of PGE2, a crucial biochemical signal mediating immune and reproductive physiology of S. exigua.

Dataset Information

Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity.

Publications

Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity.

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