Proliferation of human non-small-cell lung cancer cell lines: role of interleukin-6.
Interleukin-6 (IL-6) is involved in regulation of the immune response, acute phase reaction, and cell proliferation. The aim of this study was to investigate whether IL-6 is implicated in cell proliferation of human non-small-cell lung cancer (NSCLC) cell lines. We analyzed IL-6 messenger RNA (mRNA) and protein expression in eight NSCLC cell lines: A549, Calu3, Calu6, H23, H522, H810, H1155, and H1299. The A549, Calu3, Calu6, and H23 cell lines expressed IL-6 mRNA and protein. In these cell lines, fetal calf serum (FCS) significantly increased cell proliferation as assessed by thymidine incorporation. In the presence of IL-6 antisense oligonucleotides, both proliferation and IL-6 synthesis were downregulated. In contrast, IL-6 mRNA and protein could not be detected in the NSCLC cell lines H522, H810, H1155, and H1299. In these NSCLC cell lines, FCS only marginally increased cell proliferation and IL-6 antisense oligonucleotides did not affect cell proliferation. The addition of neither exogenous IL-6 nor neutralizing anti-IL-6 antibodies affected cell proliferation in any of the experiments. Our data thus provide evidence that intracellular IL-6 is required in the control of cell proliferation in a subset of human NSCLC cell lines. We suggest the existence of two subtypes of NSCLC, an IL-6-dependent and an IL-6-independent type.
Division of Pneumology, Department of Internal Medicine and Research, University Hospital, Basel, Switzerland.
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Bihl
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Tamm
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Nauck
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Wieland
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Perruchoud
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Roth
D000906:Antibodies / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D001798:Blood Proteins / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000737:chemistry / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D008175:Lung Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D013936:Thymidine / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D016375:Antisense Elements (Genetics); D001798:Blood Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D014316:Tritium; D013936:Thymidine