Distinct expression pattern of the full set of secreted phospholipases A ₂ in human colorectal adenocarcinomas: sPLA ₂-III as a biomarker candidate

Abstract

Recent studies suggest that secreted phospholipases A ₂ (sPLA ₂s) represent attractive potential tumour biomarkers and therapeutic targets for various cancers. As a first step to address this issue in human colorectal cancer, we examined the expression of the full set of sPLA ₂s in sporadic adenocarcinomas and normal matched mucosa from 21 patients by quantitative PCR and immunohistochemistry. In normal colon, PLA2G2A and PLA2G12A were expressed at high levels, PLA2G2D, PLA2G5, PLA2G10 and PLA2G12B at moderate levels, and PLA2G1B, PLA2G2F and PLA2G3 at low levels. In adenocarcinomas from left and right colon, the expression of PLA2G3 was increased by up to 40-fold, while that of PLA2G2D and PLA2G5 was decreased by up to 23- and 14-fold. The variations of expression for sPLA ₂-IID, sPLA ₂-III and sPLA ₂-V were confirmed at the protein level. The expression pattern of these sPLA ₂s appeared to be linked respectively to the overexpression of interleukin-8, defensin α6, survivin and matrilysin, and downregulation of SFRP-1 and RLPA-1, all these genes being associated to colon cancer. This original sPLA ₂ profile observed in adenocarcinomas highlights the potential role of certain sPLA ₂s in colon cancer and suggests that sPLA ₂-III might be a good candidate as a novel biomarker for both left and right colon cancers.