Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAM) 1, 5 and 6 as Biomarkers in Pancreatic Cancer |
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| Authors: | Florian Gebauer Daniel Wicklein Jennifer Horst Philipp Sundermann Hanna Maar Thomas Streichert Michael Tachezy Jakob R. Izbicki Maximilian Bockhorn Udo Schumacher |
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| Affiliation: | 1. Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.; 2. Institute of Anatomy and Experimental Morphology and University Cancer Center Hamburg (UCCH), University Medical-Center Hamburg-Eppendorf, Hamburg, Germany.; 3. Institute of Clinical Chemistry, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany.; Wayne State University School of Medicine, United States of America, |
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| Abstract: | BackgroundAim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 in pancreatic adenocarcinoma (PDAC).Experimental DesignCEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC) and by enzyme linked immunosorbent assays.ResultsPresence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC) and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS). The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group.ConclusionThe effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis. |
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