Midkine is up-regulated in both cancerous and inflamed bowel, reflecting lymph node metastasis in colorectal cancer and clinical activity of ulcerative colitis. (January 2017)

• Record Type: Journal Article
• Authors: Krzystek-Korpacka, Malgorzata; Gorska, Sabina; Diakowska, Dorota; Kapturkiewicz, Bartosz; Podkowik, Magdalena; Gamian, Andrzej; Bednarz-Misa, Iwona
• Is Part Of: Cytokine. Volume 89(2017)
• Page Start: 68
• Page End: 75
• Publication Date: 2017-01
• Subjects: Midkine -- Colorectal cancer -- Inflammatory bowel disease -- Ulcerative colitis -- Crohn's disease -- Surgical stress; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.09.020
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Midkine overexpression in colon and leukocytes accompanies regional metastasis in CRC. Midkine is overexpressed in inflamed bowel only in ulcerative colitis. Midkine expression in tumor-adjacent tissue is upregulated and depends on CRC stage. Serum midkine drops directly after surgery but its levels are restored on 3rd day. Abstract: Midkine is a multifunctional cytokine and growth factor displaying proinflammatory and pro-tumorigenic activity. Its association with bowel diseases has not been fully elucidated. Our purpose was to delineate midkine expression pattern by RT-qPCR in inflamed/cancerous bowel (n = 208) and whole blood (n = 150) in colorectal cancer (CRC), Crohn's disease (CD), and ulcerative colitis (UC) and to evaluate midkine dynamics in early postoperative period following colorectal surgery. The expression of midkine was significantly up-regulated in stage III CRC and independently associated with lymph node metastasis. The expression of midkine in whole blood was up-regulated solely in N1 CRC. Midkine expression in cancer-free tissue (CRC) was also elevated and dependent on CRC advancement. In IBD, inflammation increased the bowel expression of midkine solely in UC, in a manner proportional to the disease clinical activity. Large and small bowel differed with respect to the expression of midkine in quiescent tissue (higher in small bowel) and to its correlation pattern with chemokines (in a large bowel) and angiogenic factors and cell cycle regulators (in a small bowel). Circulating midkine and its expression in whole blood dropped directly following colorectal surgery; however, the concentration of midkine in serum was restored on postoperative day three. Midkine is involved in bowel inflammation in UC and lymph node metastasis in CRC, rendering midkine an attractive target for their treatment. Owing to midkine elevation in early postoperative period and its overexpression in tumor-adjacent tissue, targeting midkine might be considered also as a prevention of CRC recurrence following curative tumor resection.