CXC-Chemokine CXCL14, CXCL16 und Disintegrin-ähnliche Metalloproteinase ADAM10 — Expression, Funktion und Interaktion bei der Karzinogenese des Pankreaskarzinoms

Abstract

Background: Chemokines are a superfamily of XC-, CC-, CXC-chemokines and the CXXXC-chemokine. CXC chemokines and their receptors play a pivotal role in the regulation of growth and dissemination of tumor cells, as well as in angiogenesis and host immune response in solid malignancies. The disintegrin and metalloproteinase ADAM10 facilitates shedding of various membrane-bound proteins. The expression, function, and potential interaction of CXCL14, CXCL16 and ADAM10 in pancreatic cancer are still unknown. Methods: Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and ELISA were used to analyze expression of CXCL14, CXCL16 and ADAM10 in human pancreatic cancer cell lines and tissues of patients. Recombinant CXCL14 and CXCL16 were used to determine effects on and invasiveness of pancreatic cancer cell lines. ADAM10 siRNA transfection was performed in BxPC-3 and COLO-357 cells and CXCL16 was measured in the cell culture supernatants. Results: There was a significant increase of CXCL14, CXCL16 and ADAM10 mRNA levels in pancreatic cancer tissues compared to normal controls. In vitro, incubation of pancreatic cancer cells with rhCXCL14 and rhCXCL16 resulted in an increase of invasiveness. Silencing of ADAM10 revealed a significant reduction of soluble CXCL16, as well as less invasiveness of cancer cells. Conclusion: CXCL14, CXCL16, and ADAM10 are overexpressed in pancreatic cancer. CXCL14 and CXCL16 are potent mediators of invasiveness in pancreatic cancer cells. ADAM10 plays a role in the regulation of CXCL16 in pancreatic cancer.