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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Taoufik Nedjadi, Anthony Evans, Adnan Sheikh, Lawrence Barerra, Suliman Al-Ghamdi, Lucy Oldfield, W. Greenhalf, John P. Neoptolemos, Eithne Costello

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.
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Metadata
Title
S100A8 and S100A9 proteins form part of a paracrine feedback loop between pancreatic cancer cells and monocytes
Authors
Taoufik Nedjadi
Anthony Evans
Adnan Sheikh
Lawrence Barerra
Suliman Al-Ghamdi
Lucy Oldfield
W. Greenhalf
John P. Neoptolemos
Eithne Costello
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5161-4

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