Expression and potential function of the CXC chemokine CXCL16 in pancreatic ductal adenocarcinoma
CXC chemokines have a major influence on the angiogenesis, growth and metastatic potential of pancreatic ductal adenocarcinoma. CXCL16 is a unique transmembrane CXC chemokine, which is shed by members of the disintegrins and metalloproteases (ADAMs), in particular by ADAM10 and ADAM17. In our study, we evaluated expression and potential function of CXCL16 and its receptor CXCR6. CXCL16 and the receptor CXCR6 are upregulated in pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis tissues in contrast to normal pancreatic tissues at the mRNA and protein levels. In 85 and 100% of the investigated samples, tumor cells showed positive immuno-staining for CXCL16 and CXCR6, respectively; furthermore, tubular complexes of chronic pancreatitis and the invasive front of PDAC were immunopositive for CXCL16 and CXCR6. Stimulation of PDAC cells with proinflammatory cytokines increased CXCL16 protein levels, whereas silencing of ADAM10 with siRNA transfection led to a decrease in CXCL16 protein levels in cell culture supernatants. No effects on cell viability were notable after incubation of cancer cells with CXCL16. However, CXCL16 markedly increased invasiveness of PDAC cells. Clinically, 82.5% of PDAC patients had higher CXCL16 serum values than the highest value seen in healthy donors. SELDI-TOF-MS analysis confirmed the upregulation of CXCL16 in sera of PDAC patients. In conclusion, CXCL16 in both transmembrane and soluble forms, and its receptor CXCR6, seem to play an important role in the pathobiology of pancreatic cancer and might be potential markers for pancreatic cancer diagnosis and a target for multimodal therapy concepts in the future.
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Document Type: Research Article
Affiliations: Department of General Surgery, University of Heidelberg, D-69120 Heidelberg, Germany., Email: [email protected]
Publication date: August 1, 2008
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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