Interleukin-8 (IL-8) promoter region gene polymorphism predicts pelvic recurrence after chemo-radiation in patients with rectal cancer

Zhang, W; Lu, Bingwen; Gil, Ji; Yang, Dongyun; Groshen, Susan; Lenz, Heinz‐Josef

doi:10.1016/s0360-3016(03)01303-8

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“…From patient specimens acquired through translational and clinical trials, we have reported that genetic variations in IL-8 and CXCR2 genes profoundly affects CRC progression, drug sensitivity and tumour recurrence ( Gordon et al , 2006 ; Lurje et al , 2008 ; Schultheis et al , 2008 ; Zhang et al , 2009 ). This capacity to determine clinical outcomes highlights the evolving role of IL-8/CXCR2 as the molecular predictors of response, in particular with regards to patient responsiveness towards anti-VEGF and oxaliplatin-based chemotherapy ( Zhang et al , 2003 , 2005 , 2006 ; Vallbohmer et al , 2005 ; Gordon et al , 2006 ; Lurje et al , 2008 ). We have also identified that IL-8 may serve as a key factor capable of promoting CRC proliferation and progression by stimulating tumour cell proliferation, invasion, migration and angiogenesis ( Ning et al , 2011 ).…”

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Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis

et al. 2012

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Background:Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.Methods:A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.Results:Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.Conclusion:Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.

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