Interleukin-8/CXCL8 is a growth factor for human lung cancer cell

Department of Clinical Oncology, Institute for Cancer Studies, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
British Journal of Cancer (Impact Factor: 4.84). 11/2004; 91(11):1970-6. DOI: 10.1038/sj.bjc.6602227
Source: PubMed


Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were examined in a panel of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. Using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay, we found that all NSCLC cell lines tested produced modest or high levels of IL-8 (up to 51 ng ml(-1) 10(6) cells(-1)). Expression of CXCR1 and CXCR2 was found by RT-PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (P<0.05). Exogenous IL-8 significantly stimulated cell proliferation in four SCLC cell lines tested in a dose-dependent fashion. Cell proliferation was increased by between 18% (P<0.05) and 37% (P<0.05). Stimulation of cell proliferation by IL-8 was also demonstrated by analysis of proliferating cell nuclear antigen expression and cell cycle in H69 cells. Furthermore, we investigated which receptor(s) mediated the mitogenic function of IL-8 in lung cancer cells. We found that cell proliferation was significantly reduced by anti-CXCR1 antibody but not by anti-CXCR2 antibody. In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor.

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    • "A 20 μL portion of the RT products was then brought to a volume of 20 μL containing 10 mM of each dNTP, 1 U of Taq polymerase (Promega, Madison, USA), 10 pmol of both the upstream and downstream PCR primers, and 1 x PCR buffer (proprietary formulation supplied at pH 8.5 containing blue dye and yellow dye) provided by Promega. The primers for IL-8 are as follows: forward, 5′-ATG ACT TCC AAG CTG GCC GTG GCT-3′ and reverse, 5′-TCT CAG CCC TCT TCA AAA ACT TCT-3′ with a product of 289 bps [34]. For glyceraldehyde-3-phosphate dehydrogenase (GAPDH); the forward primer was 5′-CCAGCCGAGCCACATCGCTC-3; and the reverse primer was 5′-ATGAGCCCCAGCCTTCTCCAT-3′, giving a 390 bps PCR product. "
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    • "Subsequently, we reported that IL-8 expression is transcriptionally upregulated by oncogenic KRAS mutations in NSCLC (Sunaga et al, 2012). IL-8 is an essential proinflammatory mediator that is involved in cancer development and acts as an angiogenic growth factor that promotes cell proliferation and angiogenesis, thus contributing to the progression and metastasis of NSCLC (Smith et al, 1994; Arenberg et al, 1996; Wang et al, 1996; Yatsunami et al, 1997; Zhu et al, 2004; Boldrini et al, 2005; Luppi et al, 2007). IL-8 has also been implicated in the epithelial–mesenchymal transition and cancer cell stemness during tumour progression (Palena et al, 2012). "
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    • "Since CXCL8 is not the only chemokine expressed under such circumstances, determination of its specific role is difficult. Various signals and/or pathways induce CXCL8 expression in cancers [40]. The activation of oncogenes may be linked to inflammatory signaling via the cell-intrinsic mechanism described above. "
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