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The Proinflammatory Cytokine, IL-6, and its Interference with bFGF Signaling and PSMA in Prostate Cancer Cells

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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.

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Acknowledgments

We thank the University of Carthage (Tunisia). Awatef Ben Jemaa had a predoctoral fellowship from the University of Carthage (Tunisia) during the course of this work.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Unit of Immunology and Microbiology Environmental and Carcinogenesis (IMEC), Faculty of Sciences of Bizerte, University of Carthage, 7021, Bizerte, Zarzouna, Tunisia

    Awatef Ben Jemaa & Ridha Oueslati

  2. Department of Urology, Hospital of La Rabta Tunis, Tunis, Tunisia

    Sataa Sallami

  3. Clinical Immunology, Giovanni Battista Rossi Hospital, Verona, Italy

    Dunia Ramarli & Marco Colombatti

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  1. Awatef Ben Jemaa
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  2. Sataa Sallami
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  4. Marco Colombatti
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  5. Ridha Oueslati
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Correspondence to Ridha Oueslati.

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Ben Jemaa, A., Sallami, S., Ramarli, D. et al. The Proinflammatory Cytokine, IL-6, and its Interference with bFGF Signaling and PSMA in Prostate Cancer Cells. Inflammation 36, 643–650 (2013). https://doi.org/10.1007/s10753-012-9586-7

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  • DOI: https://doi.org/10.1007/s10753-012-9586-7

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