Midkine is up-regulated in both cancerous and inflamed bowel, reflecting lymph node metastasis in colorectal cancer and clinical activity of ulcerative colitis.
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.
Dept. of Medical Biochemistry, Wroclaw Medical University, Poland. Electronic address: malgorzata.krzystek-korpacka@umed.wroc.pl.
Malgorzata
M
Krzystek-Korpacka
Laboratory of Medical Microbiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Sabina
S
Gorska
Dept. of Gastrointestinal and General Surgery, Wroclaw Medical University, Wroclaw, Poland.
Dorota
D
Diakowska
First Dept. of Oncological Surgery of Lower Silesian Oncology Center, Wroclaw, Poland.
Bartosz
B
Kapturkiewicz
Dept. of Food Hygiene and Consumer Health, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
Magdalena
M
Podkowik
Dept. of Medical Biochemistry, Wroclaw Medical University, Poland; Wroclaw Research Center EIT+, Wroclaw, Poland.
Andrzej
A
Gamian
Dept. of Medical Biochemistry, Wroclaw Medical University, Poland.
Iwona
I
Bednarz-Misa
D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007420:Intestine, Large / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D000078792:Midkine; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D015854:Up-Regulation
C066254:MDK protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D000078792:Midkine
Colorectal cancer; Crohn’s disease; Inflammatory bowel disease; Midkine; Surgical stress; Ulcerative colitis