title: 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.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
authors.forename: Katarzyna
authors.identifier: 0000-0003-3650-9311
authors.initials: K
authors.lastname: Neubauer
authors.affiliation: Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland.
authors.forename: Iwona Bednarz
authors.initials: IB
authors.lastname: Misa
authors.affiliation: Department of Gastrointestinal and General Surgery, Wroclaw Medical University, M. Curie-Sklodowskiej 66, 50-369 Wroclaw, Poland.
authors.forename: Dorota
authors.identifier: 0000-0002-1377-5601
authors.initials: D
authors.lastname: Diakowska
authors.affiliation: First Department of Oncological Surgery, Lower Silesian Oncology Center, Plac Hirszfelda 12, 53-413 Wroclaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Kapturkiewicz
authors.affiliation: Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland ; Wroclaw Research Center EIT+, Stablowicka 147, 54-066 Wroclaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gamian
authors.affiliation: Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krzystek-Korpacka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood* / Q000473:pathology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C508585:IL1B protein, human; D053583:Interleukin-1beta; D009363:Neoplasm Proteins; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human