OP001: mRNA expression of S100A8/A9 and rage in FFPE OSCC tissues

Abstract

Introduction A pro-inflammatory heterodimer S100A8/A9 (calprotectin) of the S100 family of intracellular Ca2+binding proteins is predominantly expressed by myeloid cells and mediates chronic inflammatory diseases. Calprotectin, found to be a potent ligand for RAGE (Receptor for advanced glycation end products), amplifies inflammation by production of reactive oxygen species (ROS). Calprotectin is implicated in causing persistent activation of tumour stromal cells, promoting tumour growth and inducing tumour cell invasion and metastasis. There has been surmounting evidence linking inflammation and cancer. S100A8/A9 expression in oral cancer tissues has not been understood to a large extent. The objective of this study is to assess the levels of calprotectin and RAGE in formalin fixed paraffin embedded (FFPE) oral squamous cell carcinoma (OSCC) tissues. Methodology • FFPE tissues of OSCC, inflamed oral tissue and control: non-inflamed non-neoplastic tissues, n = 10 each, were obtained from our departmental archives. • RNA from the FFPE tissues was isolated using a Qiagen RNAeasy kit and reverse transcribed using mMLV enzyme. cDNA was used as a template for estimation of the gene expression levels using Qualitative Real time PCR technique. Results RNA from the FFPE OSCC samples were successfully isolated. The mRNA levels of calprotectin and RAGE were considerably higher than that of control tissue samples; but were significantly altered in OSCC as compared to the inflamed oral tissues. Conclusion Establishment of an inflammatory microenvironment is key to the progression of inflammation mediated OSCC. Calprotectin has been identified as an important DAMP (endogenous damage-associated molecular pattern) protein which binds to RAGE, a pattern recognition receptor. Inflammatory cytokines and S100A8/A9 seem to have a positive feedback loop in the proliferation of the tumour cells. Our study throws more light on the fact that the dichotomy of S100A8/A9 levels of the OSCC tissues shows that different levels cause the tumours to behave differently.