Kallikrein related peptidases 7 and 10 and their substrate desmoglein 3 are upregulated in early stage pancreatic cancerous lesions

Abstract Differential expression of Kallikreins (KLKs) was described for established metastatic pancreatic ductal adenocarcinoma (PDAC), but their potential as markers for early detection is not known. We have performed comprehensive in silico and in situ analyses of KLK expression in PDAC at different stages of tumor development. We found that upregulation of KLK7 and KLK10 RNA and protein occurs early in tumor development and marks carcinoma in-situ lesions (stage 0, PanIN3) and early-stage (stage 1) PDAC, while non-cancerous low grade lesions stain negative for these proteases. Moreover, both KLKs are co-expressed with desmoglein-3 (DSG3) in PDAC cell lines as well as PDAC samples from treatment naïve patients. DSG3 serves as a substrate for both KLK7 and KLK10 resulting in a 30 kDa extracellular fragment. Overall, our data suggest that analyses for expression of KLK7 and KLK10 as well as their substrates could have potential as diagnostic biomarkers to distinguish non-cancerous low-grade lesions from earliest cancerous lesions in the pancreas.