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BMC Genomics

Open Access

Role of cytokines in the interplay between cancer cells and stroma-associated monocytes

BMC Genomics201415(Suppl 2):P16

https://doi.org/10.1186/1471-2164-15-S2-P16

Published: 2 April 2014

Background

Pancreatic cancer is characterized by the presence of a highly reactive stroma [1]. The latter harbors a variety of cellular compartments including stellate cells, fibroblasts, endothelial cells and a variety of inflammatory cells such as macrophages and monocytes. Interaction between tumour cells and surrounding stromal cells (tumour micro- environment) plays an important role in pancreatic cancer progression [2]. We have previously shown that stroma-associated monocytes express low molecular weight proteins: S100A8 and S100A9 [3]. The aim of this study is to investigate the involvement of S100A8 and S100A9 proteins in the tumour-stroma crosstalk and to decipher the potential signaling mechanism.

Materials and methods

Cell culture of pancreatic cancer cells and monocytic cells, HL-60 and primary isolated human monocytes. Isolation of Conditioned medias from pancreatic cancer cells. Western blotting analysis. Cytokines multiplexing assay (27-plex, BioRad). Cell signaling assay. Luciferase assay.

Results

1- The expression of S100A8 and S100A9 in monocytes is increased in response to soluble factors in pancreatic cancer cells conditioned media.

2- Cytokine profiling of cell supernatants, using Luminex assay, showed that PCC secrete a number of cytokines and growth factors including IL-8, FGF and TNF-α.

3- S100A8 and S100A9 increased phosphorylation of MAPK, erk1/2 and p38 and activated NF-kB signaling pathways in a RAGE dependent manner.

Conclusions

S100A8 and S100A9 promote specific cytokine secretion from pancreatic cancer cells. Interestingly, a number of these cytokines, in turn, induce the secretion of S100A8 and S100A9 from monocytic cells, creating a paracrine loop. These events may create a favourable environment for tumour development and metastases.

Authors’ Affiliations

(1)
King Fahd Medical Centre
(2)
Department of Molecular and Clinical Cancer Medicine, The University of Liverpool

References

  1. Hernández-Muñoz I, Skoudy A, Real FX, Navarro P: Pancreatic ductal adenocarcinoma: cellular origin, signaling pathways and stroma contribution. Pancreatology. 2008, 8 (4-5): 462-9.View ArticlePubMedGoogle Scholar
  2. Erkan M, Reiser-Erkan C, Michalski CW, Kong B, Esposito I, Friess H, Kleeff J: The impact of the activated stroma on pancreatic ductal adenocarcinoma biology and therapy resistance. Curr Mol Med. 2012, 12 (3): 288-303.View ArticlePubMedGoogle Scholar
  3. Sheikh AA, Vimalachandran D, Thompson CC, Jenkins RE, Nedjadi T, Shekouh A, Campbell F, Dodson A, Prime W, Crnogorac-Jurcevic T, Lemoine NR, Costello E: The expression of S100A8 in pancreatic cancer-associated monocytes is associated with the Smad4 status of pancreatic cancer cells. Proteomics. 2007, 7 (11): 1929-40.View ArticlePubMedGoogle Scholar

Copyright

© Nedjadi and Costello; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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