Volume 15 Supplement 2
Role of cytokines in the interplay between cancer cells and stroma-associated monocytes
© Nedjadi and Costello; licensee BioMed Central Ltd. 2014
Published: 2 April 2014
Pancreatic cancer is characterized by the presence of a highly reactive stroma . 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 . We have previously shown that stroma-associated monocytes express low molecular weight proteins: S100A8 and S100A9 . 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.
- 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
- 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
- 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
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