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RETRACTED ARTICLE: Alpha-fetoprotein contributes to THP-1 cell invasion and chemotaxis via protein kinase and Gi-protein-dependent pathways

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This article was retracted on 20 February 2023

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Abstract

Alpha-fetoprotein (AFP) for long was known as immunomodulator and tumor marker having multifaceted actions on the activity of normal and transformed cells. In present study, we have investigated the involvement of AFP in regulation of THP-1 cell line invasion and underlying mechanisms. Treatment with human recombinant AFP causes up-regulation of MMP9 expression, chemotaxis and calcium mobilization, and increases invasion through Matrigel, with no significant impact on THP-1 cell growth or viability. Using small molecule inhibitors, we have shown that the rhAFP-induced MMP9 expression depends on the activation of ERK1,2, JNK and Akt kinases, with the involvement of NFκB and likely, AP-1 transcription factors. In contrast, inhibition of p38 kinase, but not of JNK, had dramatic suppressive effect on the rhAFP-triggered chemotaxis. In addition, rhAFP-induced MMP9 expression and calcium response were completely blocked by pertussis toxin, indicating that Gi-protein-coupled receptor(s) has a mediatory role in these processes. CCR5 chemokine receptor is the only known Gi-protein binding to AFP. The action of CCR5 inhibitor Maraviroc results in partial suppression of MMP9 up-regulation and calcium response suggesting that CCR5 might be involved in these effects.

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Acknowledgments

This work was supported by International Scientific and Technical Center (project #3808) and by Russian Foundation of Basic Research (projects #09-04-01664, 11-04-01850 and 12-04-00989). We thank Tatyana Bushueva and Yury Romanov for helping in performing experiments and preparation of this manuscript.

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Authors and Affiliations

  1. Institute of Experimental Cardiology, Cardiology Research and Production Center, Moscow, 121552, Russia

    Ekaterina Zubkova, Yelena Parfyonova & Mikhail Menshikov

  2. Institute of Immunological Engineering, Lyubuchany, Chekhov District, Moscow Region, 142380, Russia

    Lidiya Semenkova, Elena Dudich & Igor Dudich

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  1. Ekaterina Zubkova
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  2. Lidiya Semenkova
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  3. Elena Dudich
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Correspondence to Mikhail Menshikov.

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Zubkova, E., Semenkova, L., Dudich, E. et al. RETRACTED ARTICLE: Alpha-fetoprotein contributes to THP-1 cell invasion and chemotaxis via protein kinase and Gi-protein-dependent pathways. Mol Cell Biochem 379, 283–293 (2013). https://doi.org/10.1007/s11010-013-1650-6

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  • DOI: https://doi.org/10.1007/s11010-013-1650-6

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