title: The proinflammatory cytokine, IL-6, and its interference with bFGF signaling and PSMA in prostate cancer cells.
abstract: The aim of the present work was to study the expression of the proinflammatory cytokine, interleukin-6 (IL-6), mediated by bFGF signaling and its possible crosstalk with prostate-specific membrane antigen (PSMA) in LNCaP and PC3-PSMA prostate cancer cell lines. PC3 cells stably transfected with PSMA gene were used for restoring PSMA expression. LNCaP and PC3-PSMA cells were exposed to 10 ng/mL of basic fibroblast growth factor (bFGF). IL-6 production was measured by ELISA assay, and levels of PSMA expression were assessed by flow cytometry. AKT, ERK1/2, and p38 phosphorylation were detected by Western blot. bFGF enhances IL-6 production in LNCaP and PC3-PSMA prostate cancer cells. The effect of bFGF on stimulating IL-6 secretion was greater in LNCaP than in PC3-PSMA cells. In the presence of bFGF, PSMA expression was activated after 4 days of treatment in LNCaP and PC3-PSMA cells. This activation was not maintained after long term of treatment in both metastatic cell lines. Solely MAPKs pathways (ERK1/2 and p38) were activated after bFGF stimulation in both metastatic cell lines, whereas AKT did not show any activation. The interference of the proinflammatory cytokine, IL-6, with bFGF signaling and PSMA, should be of high clinical relevance in the treatment of metastatic prostate cancer. In developing novel therapeutic modalities targeting IL-6, significant attention should be given to PSMA and its inactivation to fight against prostate cancer.
authors.affiliation: Unit of Immunology and Microbiology Environmental and Carcinogenesis-IMEC, Faculty of Sciences of Bizerte, University of Carthage, 7021 Bizerte, Zarzouna, Tunisia.
authors.forename: Awatef
authors.initials: A
authors.lastname: Ben Jemaa
authors.forename: Sataa
authors.initials: S
authors.lastname: Sallami
authors.forename: Dunia
authors.initials: D
authors.lastname: Ramarli
authors.forename: Marco
authors.initials: M
authors.lastname: Colombatti
authors.forename: Ridha
authors.initials: R
authors.lastname: Oueslati
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D043425:Glutamate Carboxypeptidase II / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D015850:Interleukin-6; D016222:Fibroblast Growth Factor 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II