Biochemical and Biophysical Research Communications
IL-8 interacts with metadherin promoting proliferation and migration in gastric cancer
Introduction
IL-8 has been extensively found to be implicated in the carcinogenesis of Gastric cancer (GC) [1], [2]. Elevated IL-8, whatever on mRNA [1] or protein [3]level, has been reported to be linked with high risk of patients with GC. In addition, IL-8 as well as its receptor, that is IL-8R [4], have also been shown to be associated with GC. These previous studies could lead to the suggestion that up-regulation of IL-8 was potentially linked with GC. Several recent mechanistic studies showed that IL-8 was directly involved in the metastasis of GC [5], [6], suggesting that block of IL-8 could suppress the metastasis of GC. Despite these, the underlying mechanism through which IL-8 was shown to mediate metastasis of GC remains unknown.
Metadherin (MTDH), also known as Astrocyte elevated gene-1 (AEG-1), has been reported in recent years to be as a crucial mediator in tumor metastasis [7]. Moreover, clinical studies have found that MTDH was clinically associated with chemoresistance and poor prognosis in cancer [8], indicating that targeting of MTDH may simultaneously enhance the efficacy of chemotherapeutic treatments in addition to block metastasis. However, the underlying mechanism by which MTDH plays role in the mediation of metastasis of GC remains to be investigated.
In the present study, we for the first time showed that MTDH was able to interact with IL-8, thereby promoting the invasion of GC cells, suggesting that targeting of IL8-MTDH complex might be used as an alternative potential therapeutic strategy in the curing of GC.
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Cell culture
The human gastric cancer cell lines AGS, YCC-2, MGC803, BGC823 and SGC7901 were all obtained from American Type Culture Collection (ATCC, Manassas, VA). Of the 3 gastric cancer cell lines, AGS cell line whose p53 was wild type, whereas MGC-803 and SGC-7901 were all p53-mutant gastric cancer cell lines. 293T cells were stored in liquid nitrogen in central laboratory in our hospital. These cells were cultured in Dulbecco's modified Eagle's medium (DMEM, Invitrogen, Carlsbad, CA) supplemented with
IL-8 was commonly shown to be pronouncedly up-regulated in GC compared with paired normal control
To investigate the role IL-8 played in GC, we've detected the expression level of IL-8 in GC and paired normal control tissues using immunohistochemistry. Firstly, before undertaking experiment, to evaluate the correctness and specific of primary antibody against IL-8, pre-evaluation of specificity of IL-8 antibody to be used was carried out both on cell line and clinical tissues level using antigen pre-adsorption test approach. It was shown that the specificity of primary antibody against IL-8
Discussion
This is the first report of clinicopathological significance of IL-8 expression and biochemical interaction of IL-8 with MTDH in the setting of GC. IL-8 was shown to be significantly up-regulated in GC tissues in comparison with paired normal control tissues; and that up-regulation of IL-8 was found to be pronouncedly associated with T classification, clinical stage, lymph node metastasis, differentiation degree and inferior overall prognosis of patients with GC. In addition, we identified that
Conflict of interest
The authors have declared that there was no conflict of interest in the study.
Acknowledgements
The present study was financially supported by the department of General Surgery, The First Affiliated Hospital of Nanchang University.
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