Dynamic changes of interleukin-8 network along the colorectal adenoma–carcinoma sequence |
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Authors: | Guanglin Cui Aping Yuan Rasmus Goll Barthold Vonen Jon Florholmen |
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Institution: | 1.Laboratory of Gastroenterology, Faculty of Medicine, Institute of Clinical Medicine,University of Troms?,Troms?,Norway;2.Department of Gastroenterology,University Hospital of North Norway,Troms?,Norway;3.Department of Gastrointestinal Surgery,University Hospital of North Norway,Troms?,Norway |
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Abstract: | 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. |
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Keywords: | Chemokine Carcinogenesis Adenoma– carcinoma sequence |
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