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The elastin peptide (VGVAPG)3 induces the 3D reorganisation of PML-NBs and SC35 speckles architecture, and accelerates proliferation of fibroblasts and melanoma cells

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Abstract

During melanoma tumour growth, cancerous cells are exposed to the immediate surrounding the micro- and macro environment, which is largely modified through the degradation of the extracellular matrix by fibroblast-derived metalloproteinases. Among the degradation products, (VGVAPG)3, an elastin peptide is known to stimulate the proliferation of both fibroblasts and cancerous cells by binding to the elastin-binding receptor and activating the MEK/ERK signal transduction pathway. As this process strongly modifies mRNA synthesis, we investigated its effect on the relative three-dimensional organisation of the major partners of the mRNA splicing machinery: promyelocytic nuclear bodies (PML-NBs ) and splicing component 35 speckles (SC35) of normal fibroblasts and melanoma SK-MEL-28 cells. SC35 and PML-NBs proteins were immunolabeled and imaged by confocal microscopy within these cells cultured with (VGVAPG)3. Three-dimensional reconstruction was performed to elucidate the organisation of PML-NBs and SC35 speckles and their spatial relationship. In G0 cells, SC35 speckles were sequestered in PML-NBs. Shortly after (VGVAPG)3 stimulation, the three-dimensional organisation of PML-NBs and SC35 speckles changed markedly. In particular, SC35 speckles gradually enlarged and adopted a heterogeneous organisation, intermingled with PML-NBs. Conversely, inhibition of the elastin-binding protein or MEK/ERK pathway induced a remarkable early sequestration of condensed SC35 speckles in PML-NBs, the hallmark of splicing inhibition. The 3D architecture of speckles/PML-NBs highlights the modulation in their spatial relationship, the multiple roles of PML-NBs in activation, inhibition and sequestration, and provides the first demonstration of the dependence of PML-NBs and SC35 speckles on the elastin peptide for these functions.

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Acknowledgments

This work received financial support from Région Chanpagne-Ardenne for PhD grant of Aurore Chatron-Colliet.

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Authors and Affiliations

  1. UMR CNRS 7369 MEDyC, SFR Cap-Santé, URCA, Reims, France

    Aurore Chatron-Colliet, Nathalie Lalun, Sandrine Kurdykowski, Anthony Rusciani, Dominique Ploton, Laurent Duca & Hélène Bobichon

  2. Plateforme IBIsA, URCA, Reims, France

    Christine Terryn

  3. Laboratoire Pol Bouin, Hôpital Maison Blanche, Reims, France

    Marianne Lorenzato

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  1. Aurore Chatron-Colliet
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  2. Nathalie Lalun
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  9. Hélène Bobichon
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Correspondence to Hélène Bobichon.

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Chatron-Colliet, A., Lalun, N., Terryn, C. et al. The elastin peptide (VGVAPG)3 induces the 3D reorganisation of PML-NBs and SC35 speckles architecture, and accelerates proliferation of fibroblasts and melanoma cells. Histochem Cell Biol 143, 245–258 (2015). https://doi.org/10.1007/s00418-014-1274-2

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