S100A8 and S100A9 proteins form part of a paracrine feedback loop between pancreatic cancer cells and monocytes

Nedjadi, Taoufik, Evans, Anthony ORCID: 0000-0001-8547-1730, Sheikh, Adnan, Barerra, Lawrence, Al-Ghamdi, Suliman, Oldfield, Lucy ORCID: 0000-0002-0839-402X, Greenhalf, W, Neoptolemos, John P and Costello, Eithne (2018) S100A8 and S100A9 proteins form part of a paracrine feedback loop between pancreatic cancer cells and monocytes. BMC CANCER, 18 (1). 1255-.

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Official URL: http://dx.doi.org/10.1186/s12885-018-5161-4

Abstract

<h4>Background</h4>The secretion of soluble factors enables communication between tumour cells and the surrounding microenvironment and plays an important role in oncogenesis. Pancreatic ductal adenocarcinoma (PDAC) is characterised by a highly reactive microenvironment, harbouring a variety of cell types, including S100A8/S100A9-expressing monocytes. S100A8/S100A9 proteins regulate the behaviour of cancer cells by inducing pre-metastatic cascades associated with cancer spread. The aim of this study was to examine how S100A8/A9 proteins mediate tumour-stroma crosstalk in PDAC.<h4>Methods</h4>Cytokine profiling of pancreatic cancer cell-derived conditioned media was performed using Bio-Plex Pro 27 Plex Human Cytokine assays. Protein expression and activation of downstream signalling effectors and NF-κB were assessed by western blotting analysis and reporter assays respectively.<h4>Results</h4>Stimulation of cultured pancreatic cancer cells with S100A8 and S100A9 increased the secretion of the pro-inflammatory cytokines IL-8, TNF-α, and FGF. S100A8, but not S100A9 induced PDGF secretion. Conversely, pancreatic cancer cell-derived conditioned media and the individual cytokines, TNF-α and TGF-β induced the expression of S100A8 and S100A9 proteins in the HL-60 monocytic cell line and primary human monocytes, while FGF and IL-8 induced the expression of S100A9 only. S100A8 and S100A9 activated MAPK and NF-κB signalling in pancreatic cancer. This was partially mediated via activation of the receptor of advanced glycosylation end-product (RAGE).<h4>Conclusion</h4>S100A8 and S100A9 proteins induce specific cytokine secretion from PDAC cells, which in turn enhances the expression of S100A8/A9. This paracrine crosstalk could have implications for PDAC invasiveness and metastatic potential.

Item Type:	Article
Uncontrolled Keywords:	Pancreatic Cancer, Stroma, S100A8, S100A9, Cytokines, Monocytes
Depositing User:	Symplectic Admin
Date Deposited:	01 Feb 2019 15:29
Last Modified:	19 Jan 2023 01:05
DOI:	10.1186/s12885-018-5161-4
Open Access URL:	https://doi.org/10.1186/s12885-018-5161-4
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3032133