2. Academic Validation
  3. Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles

Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles

  • J Extracell Vesicles. 2025 Aug;14(8):e70133. doi: 10.1002/jev2.70133.
Barnabas Irmer 1 2,  Allegra Angenendt 1 2,  Luc Camoin 3,  Stéphane Audebert 3,  Christiane Geyer 4,  Mirjam Gerwing 4,  Hanna Spiessbach 1,  Mira Hebel 1,  Émilie Baudelet 3,  Darius Wlochowitz 5,  Uwe Hansen 6,  Annalen Bleckmann 1 2,  Pascale Zimmermann 7 8,  Kerstin Menck 1 2 7 9
Affiliations

Affiliations

  • 1 Department of Medicine A, Hematology, Oncology, and Pneumology, University of Muenster, Muenster, Germany.
  • 2 West German Cancer Center, University Hospital Muenster, Muenster, Germany.
  • 3 Marseille Proteomics Platform, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, Inserm, CNRS, Marseille, France.
  • 4 Clinic for Radiology, University of Muenster, Muenster, Germany.
  • 5 Department of Medical Bioinformatics, University Medical Center Goettingen, Goettingen, Germany.
  • 6 Institute for Musculoskeletal Medicine, University of Muenster, Muenster, Germany.
  • 7 Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille Université, Inserm, CNRS, Marseille, France.
  • 8 Department of Human Genetics, K. U. Leuven, Leuven, Belgium.
  • 9 Clinic for Hematology/Medical Oncology, University Medical Center Goettingen, Goettingen, Germany.
PMID: 40831280 DOI: 10.1002/jev2.70133
Abstract

Despite extensive proof for the tumour-supporting function of cancer-derived small extracellular vesicles (sEVs), attributions of pathological effects to specific sEV subpopulations are poorly described. In this study, we aimed to characterise a distinct sEV species under the control of Syntenin, a key regulator of endosomal sEV biogenesis, regarding its proteomic cargo and pro-tumourigenic functions. Using mass spectrometry (MS), we detected 178 down- and 236 up-regulated proteins on sEVs from breast Cancer cells upon Syntenin knockout (KO). Pathway enrichment analysis suggested that Syntenin depletion was particularly associated with adhesion-related processes. Accordingly, sEVs from Syntenin-deficient 4T1 and MCF-7 breast Cancer cells showed a reduced expression of several focal adhesion and cell-cell junction proteins. Syntenin silencing reduced the Fibronectin-binding capacity of sEVs from both cell lines, which was mediated by sEV-associated Integrin alpha-V/beta-3 (αVβ3). Compared to sEVs from wildtype cells, Syntenin KO sEVs showed decreased tropism towards the Fibronectin-rich liver microenvironment in vivo, provided less adhesive support for 4T1 cells and thereby failed to induce Cancer cell migration, which appeared to be independent of EV uptake. In summary, this study revealed that Syntenin has a large-scale effect on the proteomic cargo of sEVs and regulates their adhesive, organotropic and pro-migratory properties in breast Cancer.

Keywords

Syntenin; adhesion; breast cancer; cell migration; extracellular vesicles; integrins.

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