Plasma-derived small extracellular vesicles unleash the angiogenic potential in head and neck cancer patients

Luisa Tengler; Julia Schütz; Moritz Tiedtke; Jadwiga Jablonska; Marie-Nicole Theodoraki; Katja Nitschke; Christel Weiß; Elena Seiz; Annette Affolter; Frederic Jungbauer; Anne Lammert; Nicole Rotter; Sonja Ludwig

doi:10.1186/s10020-023-00659-w

Molecular Medicine (May 2023)

Plasma-derived small extracellular vesicles unleash the angiogenic potential in head and neck cancer patients

Luisa Tengler,
Julia Schütz,
Moritz Tiedtke,
Jadwiga Jablonska,
Marie-Nicole Theodoraki,
Katja Nitschke,
Christel Weiß,
Elena Seiz,
Annette Affolter,
Frederic Jungbauer,
Anne Lammert,
Nicole Rotter,
Sonja Ludwig

Affiliations

Luisa Tengler: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Julia Schütz: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Moritz Tiedtke: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Jadwiga Jablonska: Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen
Marie-Nicole Theodoraki: Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center
Katja Nitschke: Department of Urology and Urosurgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Christel Weiß: Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Elena Seiz: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Annette Affolter: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Frederic Jungbauer: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Anne Lammert: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Nicole Rotter: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
Sonja Ludwig: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg

DOI: https://doi.org/10.1186/s10020-023-00659-w
Journal volume & issue: Vol. 29, no. 1
pp. 1 – 14

Abstract

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Abstract Background In Head and neck cancer (HNC) angiogenesis is essential for tumor progression and metastasis. Small extracellular vesicles (sEVs) from HNC cell lines alter endothelial cell (EC) functions towards a pro-angiogenic phenotype. However, the role of plasma sEVs retrieved from HNC patients in this process is not clear so far. Methods Plasma sEVs were isolated on size exclusion chromatography columns from 32 HNC patients (early-stage UICC I/II: 8, advanced-stage UICC III/IV: 24), 12 patients with no evident disease after therapy (NED) and 16 healthy donors (HD). Briefly, sEVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), BCA protein assays and Western blots. Levels of angiogenesis-associated proteins were determined using antibody arrays. The interaction of fluorescently-labeled sEVs with human umbilical vein ECs was visualized by confocal microscopy. The functional effect of sEVs on tubulogenesis, migration, proliferation and apoptosis of ECs was assessed. Results The internalization of sEVs by ECs was visualized using confocal microscopy. Based on antibody arrays, all plasma sEVs were enriched in anti-angiogenic proteins. HNC sEVs contained more pro-angiogenic MMP-9 and anti-angiogenic proteins (Serpin F1) than HD sEVs. Interestingly, a strong inhibition of EC function was observed for sEVs from early-stage HNC, NED and HD. In contrast, sEVs from advanced-stage HNC showed a significantly increased tubulogenesis, migration and proliferation and induced less apoptosis in ECs than sEVs from HD. Conclusions In general, plasma sEVs carry a predominantly anti-angiogenic protein cargo and suppress the angiogenic properties of ECs, while sEVs from (advanced-stage) HNC patients induce angiogenesis compared to HD sEVs. Thus, tumor-derived sEVs within the plasma of HNC patients might shift the angiogenic switch towards angiogenesis.

Published in Molecular Medicine

ISSN: 1076-1551 (Print); 1528-3658 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology; Science: Chemistry: Organic chemistry: Biochemistry
Website: https://molmed.biomedcentral.com

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