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BioMed Research International
Volume 2015, Article ID 523930, 12 pages
http://dx.doi.org/10.1155/2015/523930
Research Article

Nampt/PBEF/Visfatin Upregulation in Colorectal Tumors, Mirrored in Normal Tissue and Whole Blood of Colorectal Cancer Patients, Is Associated with Metastasis, Hypoxia, IL1β, and Anemia

1Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
2Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland
3Department of Gastrointestinal and General Surgery, Wroclaw Medical University, M. Curie-Sklodowskiej 66, 50-369 Wroclaw, Poland
4First Department of Oncological Surgery, Lower Silesian Oncology Center, Plac Hirszfelda 12, 53-413 Wroclaw, Poland
5Wroclaw Research Center EIT+, Stablowicka 147, 54-066 Wroclaw, Poland

Received 5 February 2015; Revised 20 April 2015; Accepted 23 April 2015

Academic Editor: Andreas Jenke

Copyright © 2015 Katarzyna Neubauer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Targeting Nampt/PBEF/visfatin is considered a promising anticancer strategy, yet little is known about its association with colorectal cancer (CRC). We quantified Nampt/PBEF/visfatin expression in bowel and blood (mRNA and protein), referring it to CRC advancement and inflammatory, angiogenic, hypoxia, and proliferation indices. Tumor Nampt/PBEF/visfatin upregulation was associated with metastasis, anemia, tumor location, HIF1α, and inflammatory and angiogenic indices, of which HIF1α, IL1β, and anemia explained 70% in Nampt/PBEF/visfatin variability. Nampt/PBEF/visfatin expression in nontumor tissue, both mRNA and protein, increased in patients with metastatic disease and mild anemia, and, on transcriptional level, correlated with HIF1α, IL1β, IL8, CCL2, and CCL4 expression. Whole blood Nampt/PBEF/visfatin tended to be elevated in patients with metastatic cancer or anemia and correlated with inflammatory indices, of which IL1β, IL8, and hematocrit explained 60% of its variability. Circulating visfatin was associated with lymph node metastasis and inflammatory and angiogenic indices. In vitro experiments on SW620 cells demonstrated Nampt/PBEF/visfatin downregulation in response to serum withdrawal but its upregulation in response to serum induction and hypoxia. Stimulation with recombinant visfatin did not provide growth advantage. Summarizing, our results link Nampt/PBEF/visfatin with tumor metastatic potential and point at inflammation and hypoxia as key inducers of its upregulation in CRC.