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


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.


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.


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.


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Correspondence to Taoufik Nedjadi.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Nedjadi, T., Costello, E. Role of cytokines in the interplay between cancer cells and stroma-associated monocytes. BMC Genomics 15 (Suppl 2), P16 (2014).

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