Pancreatic Cancer Cell Lines Can Induce Prostaglandin E2 Production from Human Blood Mononuclear Cells

Svitlana P Grekova,Zahari Raykov,Laurent Daeffler,Assia Angelova

doi:10.1155/2011/741868

Svitlana P Grekova, Zahari Raykov + Show 2 more

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https://doi.org/10.1155/2011/741868

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Abstract

Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2) in the pathogenesis of a wide range of malignancies. The protumorigenic properties of COX-2 are generally thought to be mediated by its product, PGE2, which is shown to promote tumor spread and growth by multiple mechanisms but most importantly through modulation of the local immune response in the tumor. Pancreatic tumor cells produce various amounts of PGE2, some of them being even deficient in COX enzymes or other PGE2 synthases. Here we describe that, beside pancreatic tumor cells or stromal fibroblasts, human peripheral blood mononuclear cells can also produce PGE2 upon coculture with pancreatic cancer cells. Stimulating of cellular cPLA2 within PBMCs by secreted factors, presumably sPLA2, from tumor cells appeared crucial, while the direct contact between PBMCs and PDACs seemed to be dispensable for this effect. Our data is emphasizing the complex interactions participating in the formation of the tolerogenic immune milieu within pancreatic tumors.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal gastrointestinal malignancies
We describe that the culture of human pancreatic cancer cells with peripheral blood mononuclear cells induces the release of PGE2 irrespective of the COX status and PGE2 producing capacity of the PDAC cell line used in the assay
BxPC-3 have been formerly reported to intrinsically produce PGE2, since they are endowed with several active elements of the PGE2 enzymatic cascade, namely, cytoplasmic phospholipase A2 (cPLA2), COX-1, and COX-2 [12]

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal gastrointestinal malignancies. One of the main representatives of prostaglandins is PGE2, characterized as a mediator with suppressive activity at several levels of the immune response [5] It selectively impairs the production of interleukin-2 (IL-2) and interferon-γ (IFNγ) in T cells, blocks the production of dendritic-cell- (DC-) produced proinflammatory cytokines, including IL-12p70, and induces IL-10 production [6,7,8]. It has to be noted that, beside PSCs, other cells types such as macrophages, dendritic cells, and lymphocytes that infiltrate pancreatic carcinoma tissue actively participate in the formation of the cellular and cytokine milieu within the tumor [15] These cells are considered to be quickly suppressed by the tolerogenic microenvironment of the PDAC tumor, for which PGE2 seems to play an important role [16]. We describe that the culture of human pancreatic cancer cells (or their conditioned media) with peripheral blood mononuclear cells induces the release of PGE2 irrespective of the COX status and PGE2 producing capacity of the PDAC cell line used in the assay

Materials and Methods

Results and Discussion

Conclusion