title: Interleukin-1beta and tumour necrosis factor-alpha promote the transformation of human immortalised mesothelial cells by erionite.
abstract: Asbestos fails to induce the transformation of human mesothelial cells in vitro although it has been known as a potential carcinogen to human mesothelial cells. Interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) are major cytokines released by macrophages after inhalation of asbestos. These cytokines can regulate mesothelial cell proliferation both in vitro and in vivo. In the present study, we used the growth in soft agar as an index of transformation and investigated the role of IL-1beta and TNF-alpha during the process of human mesothelial cell carcinogenesis. Both IL-1beta and TNF-alpha were demonstrated to enhance erionite-induced transformation of the immortalised, non-tumorigenic human mesothelial cell line (MeT-5A) in vitro. The MeT-5A cells could only be transformed when the cells were exposed to a combination of cytokines and erionite, or at least two cytokines together without erionite, for at least 4 months in vitro. The findings presented here suggest that IL-1beta and TNF-alpha play a significant role in the pathogenesis of mesothelioma, and that it might be desirable to block or inhibit cytokine secretion in high risk populations to prevent mesothelioma.
authors.affiliation: Molecular Oncology Unit, Cancer Research UK, Imperial College London Hammersmith Hospital, London W12 0NN, UK. yaohe.wang@cancer.org.uk
authors.forename: Yaohe
authors.initials: Y
authors.lastname: Wang
authors.forename: Steven P
authors.initials: SP
authors.lastname: Faux
authors.forename: Gunnel
authors.initials: G
authors.lastname: Hallden
authors.forename: David H
authors.initials: DH
authors.lastname: Kirn
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Houghton
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Lemoine
authors.forename: Graham
authors.initials: G
authors.lastname: Patrick
mesh_terms: D002461:Cell Line, Transformed; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D017641:Zeolites / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C083174:erionite; D017641:Zeolites