Saudi Journal of Gastroenterology
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Year : 2011  |  Volume : 17  |  Issue : 3  |  Page : 163-164
Serum vascular endothelial growth factor and interleukin-6 in colorectal cancer

Associate Professor of Physiology, Gastrointestinal Physiology, College of Medicine, King Saud University, Saudi Arabia

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Date of Web Publication4-May-2011

How to cite this article:
Alzoghaibi M. Serum vascular endothelial growth factor and interleukin-6 in colorectal cancer. Saudi J Gastroenterol 2011;17:163-4

How to cite this URL:
Alzoghaibi M. Serum vascular endothelial growth factor and interleukin-6 in colorectal cancer. Saudi J Gastroenterol [serial online] 2011 [cited 2020 Aug 9];17:163-4. Available from:

Colorectal cancer remains a major health concern in the Western world. It represents the fourth most common cause of cancer-related death. [1] Aging, inflammatory bowel disease, certain hereditary conditions, and a family history of colorectal cancer are the most common risk factors for colorectal cancer. Approximately 6% of colorectal cancers can be attributed to recognizable heritable gene mutations. [2]

Development of human tumors requires a newly formed vascular network. [3] Metastases have shown to be correlated with an increased vascular density; therefore, the inhibition of tumor angiogenesis will arrest tumor growth and decrease metastatic potential. Several growth factors have been shown to stimulate angiogenesis. Vascular endothelial growth factor (VEGF) seems to play a pivotal role in the proliferation and development of endothelial cells, providing blood supply to the tumor cells. [4] Several studies have shown an association between VEGF expression and tumor proliferation both in experimental and human models. [5],[6]

Angiogenesis is under the control of several growth factors and cytokines, [7] and the unbalance between stimulator and inhibitor factors is responsible for switching the angiogenic potential of the tumors. VEGF and its receptors are frequently overexpressed in human tumors, including the breast, nonsmall cell lung, colorectal, and prostate cancers, [8] suggesting an association of VEGF with a malignant phenotype. An expression of VEGF mRNA and protein has shown to be associated with tumor progression and poor prognosis of colon carcinoma. [9] The prognosis of advanced colon carcinoma has been attributed to VEGF. [10] Increased levels of VEGF were shown to be related with poor relapse-free and overall survival. [11] Therefore, VEGF may play an important role in determining the risk, prognosis, and survival in colorectal cancer patients.

Patients with chronic inflammation are at increased risk of developing colon cancer. [12] Growing evidence suggests that tumors are promoted by inflammatory signals from the surrounding microenvironment. The immune cells contributing to the pathology of chronic inflammation, such as neutrophils, produce inflammatory cytokines that may influence the carcinogenesis process. [13] Proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), have been suggested to regulate tumor growth during colitis-associated tumorigenesis. [13] It has been suggested that the signaling pathway via TNF-α/nuclear factor kappaB (NFκB) may be directly involved in colitis-associated carcinogenesis. [14] Popivanova and colleagues have demonstrated that TNF-α, through its effects on the immune system, plays a critical role in promoting neoplastic transformation. [15] Burstein et al. have indicated that cyclooxygenase-2 and nuclear factor kappaB provide an important link between inflammation and cancer and are targets for chemoprevention therapy. [16]

Recent studies have described the importance of IL-6 and its downstream molecules such as STAT3 in colitis-associated colon cancer and their emerging as potential targets for anticancer therapy. [12],[17] Chan et al. have demonstrated that plasma levels of TNF receptor 2, but not IL-6, are associated with an increased risk of colorectal cancer. [18] In consistent to the current study, Knüpfer and Preiss have shown that colon cancer patients reveal higher serum IL-6 levels than healthy subjects that were associated with increasing tumor stages and size. [19]

In summary, the current study[20] and others showed that plasma levels of VEGF and inflammatory cytokines, TNF-α and IL-6, may be important diagnostic indicators for colorectal cancer. While some proinflammatory cytokines promote tumor growth, such as IL-6, further studies are needed in order to elucidate the exact role of inflammatory cascade in the cellular level and colitis-associated carcinogenesis.

   References Top

1.Aiello M, Vella N, Cannavò C, Scalisi A, Spandidos DA, Toffoli G, et al. Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review). Mol Med Report 2011;4:203-8.  Back to cited text no. 1
2.Jeter JM, Kohlmann W, Gruber SB. Genetics of colorectal cancer. Oncology (Williston Park) 2006;20:269-76.   Back to cited text no. 2
3.Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990;82:4-6.  Back to cited text no. 3
4.Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res 2000;55:15-35.  Back to cited text no. 4
5.Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: A systematic review with meta-analysis. J Thorac Oncol 2009;4:1094-103.   Back to cited text no. 5
6.Yuan A, Yu CJ, Kuo SH, Chen WJ, Lin FY, Luh KT, et al. Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J Clin Oncol 2001;19:432-41.  Back to cited text no. 6
7.Bicknell R and Harris AL. Novel growth regulatory factors and tumour angiogenesis. Eur J Cancer 1991;27:781-5.  Back to cited text no. 7
8.Heist RS, Zhai R, Liu G, Zhou W, Lin X, Su L, et al. VEGF polymorphisms and survival in early-stage non-small-cell lung cancer. J Clin Oncol 2008;26:856-62.  Back to cited text no. 8
9.Lurje G, Zhang W, Schultheis AM, Yang D, Groshen S, Hendifar AE, et al. Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer. Ann Oncol 2008;19:1734-41.  Back to cited text no. 9
10.Kaio E, Tanaka S, Kitadai Y, Sumii M, Yoshihara M, Haruma K, et al. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 2003;64:61-73.  Back to cited text no. 10
11.Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 2006;94:1823-32.  Back to cited text no. 11
12.Klampfer L, Cytokines, Inflammation and Colon Cancer, Curr Cancer Drug Targets. 2011 Jan 19. [Epub ahead of print].   Back to cited text no. 12
13.Kraus S, Arber N. Inflammation and colorectal cancer. Curr Opin Pharmacol 2009;9:405-10.  Back to cited text no. 13
14.Onizawa M, Nagaishi T, Kanai T, Nagano K, Oshima S, Nemoto Y, et al. Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. Am J Physiol Gastrointest Liver Physiol 2009;296:G850-9.  Back to cited text no. 14
15.Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, et al. Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest 2008;118:560-70.  Back to cited text no. 15
16.Burstein E, Fearon ER. Colitis and cancer: A tale of inflammatory cells and their cytokines. J Clin Invest 2008;118:464-7.  Back to cited text no. 16
17.Bromberg J, Wang TC. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 2009;15:79-80.   Back to cited text no. 17
18.Chan AT, Ogino S, Giovannucci EL, Fuchs CS. Inflammatory markers are associated with risk of colorectal cancer and chemopreventive response to anti-inflammatory drugs. Gastroenterology 2011;140:799-808.  Back to cited text no. 18
19.Knüpfer H, Preiss R. Serum interleukin-6 levels in colorectal cancer patients-a summary of published results. Int J Colorectal Dis 2010;25:135-40.  Back to cited text no. 19
20.Eldesoky A, Shouma A, Mosaad Y, Elhawary A. Clinical relevance of serum vascular endothelial growth factor and Interleukin-6 in patients with colorectal cancer. Saudi J Gastroenterol 2011;17:170-3.  Back to cited text no. 20
[PUBMED]  Medknow Journal  

Correspondence Address:
Mohammad Alzoghaibi
Associate Professor of Physiology, Gastrointestinal Physiology, College of Medicine, King Saud University
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-3767.80376

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