title: A two-way interaction between hepatocyte growth factor and interleukin-6 in tissue invasion of lung cancer cell line.
abstract: Although both hepatocyte growth factor (HGF) and interleukin (IL)-6 play important roles in invasion of cancer cells, interaction between these two critical factors has not been well elucidated. In the present study we demonstrated a two-way interaction between HGF and IL-6 in in vitro invasion of a lung cancer cell line. A549 lung adenocarcinoma cells were stimulated with IL-6, and this treatment induced an upregulation of c-Met/HGF receptor mRNA expression in the cells. In addition, IL-6 enhanced the HGF-induced in vitro cell invasion. This effect was abolished by pretreatment of the cells with either anti-IL-6 neutralizing antibody or with anti-c-Met/HGF receptor blocking antibody. We also found that HGF upregulated the expression of IL-6 receptor mRNA in the same cell line, and that this upregulation enhanced the IL-6-induced cell invasion. Finally, costimulation with HGF and IL-6 showed an additive effect on invasion, and this effect was mediated by production of matrix metalloproteinase (MMP)-2 and MMP-9. These results suggest that HGF and IL-6 upregulate each other's receptors, and thus would cooperatively enhance tissue invasion. They also suggest an "autocrine circuit" among cytokines and growth factors in certain cancer cells which functions to accelerate their biologic activities such as metastatic property.
authors.affiliation: Pulmonary Section, Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: To
authors.forename: Makoto
authors.initials: M
authors.lastname: Dohi
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Tanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakagome
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D003043:Cocarcinogenesis; D016895:Culture Media, Serum-Free; D004357:Drug Synergism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016895:Culture Media, Serum-Free; D015850:Interleukin-6; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020782:Matrix Metalloproteinases