Dynamic changes of interleukin-8 network along the colorectal adenoma-carcinoma sequence.
The interleukin-8 (IL-8) network is involved in the colorectal cancer (CRC) progression. However, its role during the adenoma-carcinoma transition to date has not been fully investigated. To evaluate the dynamic changes of IL-8 network along the colorectal adenoma-carcinoma sequence, we examined the tissue IL-8 mRNA level in colorectal biopsies from 53 colorectal adenomas, 44 CRCs and 18 controls by quantitative real-time PCR (Q-PCR), and the expressions of IL-8 and its receptors (IL-8RA and IL-8RB) in the tumor microenvironment by immunohistochemistry (IHC) and double IHCs. The results showed that the tissue IL-8 mRNA level began to increase in the precancerous lesions (adenomas) as compared with the controls and became even higher in the CRCs. Significantly, the increase of IL-8 mRNA levels was associated with the increase of dysplastic grades in the adenomas, and also paralleled to the increase of Duke's stages in the CRCs. IHC results revealed that IL-8 and its receptors, IL-8RA and IL-8RB, were observed both in the stroma and in the adenomatous/cancerous cells. By double IHCs, the IL-8 expression was characterized in macrophages, lymphocytes and myofibroblasts in the tumor stroma. Further double IHC identified the co-expression of IL-8 receptors (IL-8RA and IL-8RB) with CD34 positive tumor-associated microvessels in both the adenomas and CRCs. We, therefore, conclude that activated IL-8 network in the tumor microenvironment may function as a significant regulatory factor for the adenoma progression and the adenoma-carcinoma transition.
Cui
Guanglin
G
Laboratory of Gastroenterology, Faculty of Medicine, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway. guanglin.cui@yahoo.com
Yuan
Aping
A
Goll
Rasmus
R
Vonen
Barthold
B
Florholmen
Jon
J
D000236:Adenoma / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D016209:Interleukin-8; D012333:RNA, Messenger