1. ¹Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstrasse 74, Dresden 01307, Germany
2. ²Department of Nephropathology, Evangelismos Hospital, Phedriadon 109, Athens 11364, Greece
3. ³Bioinformatics Group, Biotechnological Centre, Technical University Dresden Tatzberg 47/49, Dresden 01307, Germany
4. ⁴Division of Molecular Oncology, Clinic for General Surgery and Thoracic Surgery, Schleswig–Holstein University Hospitals, Arnold-Heller-Str. 7, Kiel 24105, Germany
5. ⁵Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada

Correspondence: Dr F Rückert, Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Haus 91, MTZ, Fetscherstr. 74, 1099 Dresden. E-mail: Felix.Rueckert@uniklinikum-dresden.de

⁶These two authors shares the senior authorship.

Received 27 June 2008; Revised 5 September 2008; Accepted 17 September 2008; Published online 14 October 2008.

Abstract

Kallikreins play an important role in tumour microenvironment and as cancer biomarkers in different cancer entities. Previous studies suggested an upregulation of KLK10 and KLK6 in pancreatic ductal adenocarcinoma (PDAC). Therefore, we evaluated the clinicopathological role of these kallikreins and their value as biomarkers in PDAC.

Differential expression was validated by DNA-microarrays and immunohistochemistry in normal and malignant pancreatic tissues. Sera concentrations of both kallikreins were evaluated using ELISA. In silico analysis of possible protein interactions and gene silencing of KLK10 in vitro using siRNAs gave further insights in the pathomechanisms.

Gene expression analysis and immunohistochemistry demonstrated a strong expression for KLK10 and KLK6 in PDAC. Statistical analysis showed that co-expression of these kallikreins correlated with an R1-resection status (P=0.017) and worse outcome for overall survival (P=0.031). Multivariate analysis proofed that co-expression is an independent prognostic factor for survival (P=0.043). Importantly, KLK10 knockdown in AsPC-1 cells significantly reduced cell migration, whereas computational analysis suggested interaction of KLK6 with angiogenetic factors as an important mechanism.

Co-expression of KLK10 and KLK6 plays an unfavourable role in PDAC. Our results suggest that this effect is likely mediated by an interaction with the factors of the extracellular matrix and enhancement of cancer cell motility.