title: Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide.
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.
authors.affiliation: .
authors.forename: Jessica
authors.initials: J
authors.lastname: Nüße
authors.affiliation: .
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Blumrich
authors.affiliation: .
authors.forename: Ursula
authors.initials: U
authors.lastname: Mirastschijski
authors.affiliation: .
authors.forename: Lennart
authors.initials: L
authors.lastname: Kappelmann
authors.affiliation: .
authors.forename: Sørge
authors.initials: S
authors.lastname: Kelm
authors.affiliation: .
authors.forename: Frank
authors.initials: F
authors.lastname: Dietz
mesh_terms: D019898:Autocrine Communication; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019899:Paracrine Communication; D010446:Peptide Fragments / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D014158:Transcription, Genetic
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; C051610:hepatoma-derived growth factor
keywords: HDGF isoforms; N-terminus; exosomes; hepatoma-derived growth factor; intra- and extra-exosomal localisation; unconventional secretion