Startseite Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide
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Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide

  • Jessica Nüße , Eva-Maria Blumrich , Ursula Mirastschijski , Lennart Kappelmann , Sørge Kelm und Frank Dietz EMAIL logo
Veröffentlicht/Copyright: 7. Dezember 2016

Abstract

Hepatoma-derived growth factor (HDGF) is a protein with diverse intracellular functions. Moreover, after non-conventional secretion, extracellular HDGF is able to influence different signaling pathways, leading for example to induction of processes like epithelial-mesenchymal transition (EMT) and cell migration. Intriguingly, in recent proteome studies, HDGF was also found secreted by special microvesicles called exosomes. Recently, we demonstrated the existence of two new HDGF isoforms (B and C). These isoforms are involved in different cellular processes than HDGF-A. Along this line, in the present study we discovered that full length HDGF-A clearly is located inside of exosomes, whereas the isoforms HDGF-B and HDGF-C are found exclusively on the outer surface. Furthermore, while HDGF-B and HDGF-C seem to use exosomes mediated pathway exclusively, HDGF-A was found also as unbound protein in the conditioned media. The new finding of an intra- or extra-exosomal localisation of protein splice variants opens a fascinating new perspective concerning functional diversity of HDGF isoforms. Dysregulation of HDGF expression during cancer development and tumor progression is a commonly known fact. With our new findings, unraveling the potential functional impact according to physiological versus pathophysiologically altered levels and compositions of intra- and extra-exosomal HDGF has to be addressed in future studies.

Acknowledgments

We would like to thank Prof. Jörn Bullerdiek, Centre for Human Genetics, University of Bremen, Germany and Prof. Dr. Martin Götte, Department of Gynecology and Obstetrics, University Medical Centre Münster, Germany for providing the cell lines MCF-7 and MDA-MB-231, respectively. Furthermore we would like to thank Dr. Jan Köser from the Centre for Chemical Analysis at the Center for Environmental Research and Sustainable Technology (UFT) Bremen. The research leading to these results has received funding from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 243195.

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Received: 2016-10-21
Accepted: 2016-12-5
Published Online: 2016-12-7
Published in Print: 2017-6-27

©2017 Walter de Gruyter GmbH, Berlin/Boston

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