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

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: 4.82). 11/2004; 91(11):1970-6. DOI: 10.1038/sj.bjc.6602227
Source: PubMed

ABSTRACT 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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    ABSTRACT: Krishna C. Majumdar was born at Bikrampur, Dhaka (now in Bangladesh). He received his B.Sc. (1966) and M.Sc. (1968) degrees from the University of Calcutta and Ph.D. (1972) from the University of Idaho under the direction of Professor B.S. Thyagarajan and continued in the same University as a research associate till mid-1974. He also carried out postdoctoral work (University of Alberta) with Professor J.W. Lown till mid-1977. He is with the University of Kalyani, lecturer (1977), reader (1984), Professor (1995-2010), and presently an UGC Emeritus Fellow at the same University. He had also served North-Eastern Hill University as a visiting Professor (1996), Indian Institute of Technology (Kharagpur) as Assoc. Professor during 1990-1991, and Tezpur University (2010) as professor of Eminence. His research interests center around synthetic organic chemistry with nearly 400 publications including review articles and book chapters. He has also edited a Wiley-VCH publication ‘Heterocycles in natural product synthesis’. His recent research interests include design and synthesis of liquid crystals. He is a fellow of the West Bengal Academy of Science and Technology, and recipient of the Chemical Research Society of India medal (2004) and Indian Chemical Society award (2006).
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