The expression of S100A8 in pancreatic cancer‐associated monocytes is associated with the Smad4 status of pancreatic cancer cells

Abstract

The cross-talk between tumour cells and the surrounding supporting host cells (stroma) is a key regulator of cancer growth and progression. By undertaking 2-DE analysis of laser capture microdissected malignant and stromal components of pancreatic tumours and benign ductal elements, we have identified high levels of S100A8 and S100A9 in tumour-associated stroma but not in benign or malignant epithelia. Immunohistochemical analysis (n = 71 patients) revealed strong expression of both proteins in stromal myeloid cells, subsequently identified as CD14(+)/CD68(- )monocytes/macrophages. Co-immunofluorescence revealed that S100A8 was expressed in a subset of S100A9-positive cells. Correlation of the expression of S100A8 and S100A9 to patient parameters revealed that the microenvironments of tumours which lacked expression of the tumour suppressor protein, Smad4, had significantly reduced numbers of S100A8-immunoreactive (p = 0.023) but not S100A9-immunoreactive (p = 0.21) cells. The ratio of S100A8- to S100A9-positive cells within individual tumours was significantly lower in Smad4-negative tumours than in Smad4-positive tumours (p<0.003). Pancreatitic specimens also contained S100A8- and S100A9-expressing cells, although this was not observed in regions displaying extensive fibrosis. In conclusion, our study provides an extensive analysis of S100A8 and S100A9 in pancreatic disease and highlights a potentially important relationship between pancreatic cancer cells and their surrounding microenvironment.

Fibroblast Growth Factor Receptor 2–Positive Fibroblasts Provide a Suitable Microenvironment for Tumor Development and Progression in Esophageal Carcinoma

“…One recent report found that S100A8 secreted by a distant primary tumor could attract Mac 1(+)-myeloid cells to the premetastatic lung, suggesting that S100A8 plays a role in long distance metastasis (40). Another study found that up-regulation of S100A8 could be detected only in tumor-associated stroma and not in malignant epithelia (41). These findings suggest that up-regulation of immune response genes in TFs could provide a suitable microenvironment for tumor cells.…”

Increased expression and phosphorylation of the two S100A9 isoforms in mononuclear cells from patients with systemic lupus erythematosus: A proteomic signature for circulating low-density granulocytes

“…However, in Smad4-negative tumors, the recruited myeloid cells express S100A9, but exhibit lower S100A8 expression [37], as it occurs in acute inflammatory reactions [38]. In SLE PBMCs the S100A9:A8 ratio was significantly higher than that in Normal PBMCs (Fig.…”

S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

“…Immunoprecipitated proteins were separated by 2-D gel electrophoresis as described earlier (Shekouh et al, 2003;Sheikh et al, 2007). Gel images were captured on a GS-800 gel scanner (BioRad, Hertfordshire, UK) and analysed using Progenesis software (NonLinear Dynamics, Newcastle upon Tyne, UK).…”

“…Gel images were captured on a GS-800 gel scanner (BioRad, Hertfordshire, UK) and analysed using Progenesis software (NonLinear Dynamics, Newcastle upon Tyne, UK). Protein spots were excised, destained, trypsin digested and subjected to MALDI-TOF MS and/or LC-MS/MS as described earlier (Shekouh et al, 2003;Sheikh et al, 2007). Data were again submitted to Mascot and the NCBI database searched with the MS tolerance set to 1.2 Da and the MS/MS tolerance to 0.6 Da, with carbamidomethyl as a fixed modification.…”