Stage-dependent Effects of Plasma Exosomes from Head and Neck Cancer Patients on Endothelial Cell Function

Introduction Angiogenesis plays an important role in the carcinogenesis, promotion and progression of head and neck cancer (HNC). While exosomes from HNC cell lines effectively reprogram endothelial cells (ECs) to promote angiogenesis, the role of plasma exosomes is still unclear.

Materials & Methods Exosomes were isolated from plasma of 32 HNC patients (UICC I/II: 7, UICC III/IV: 25 patients), 12 recovered patients (NED) and 15 healthy donors (HD) using size-exclusion chromatography. The interaction of exosomes with ECs was visualized by confocal microscopy (CM). Exosomal protein content was examined by Western blots and angiogenesis-associated proteins were detected on antibody arrays. To analyze the angiogenic effect of exosomes, tubulogenesis, migration, proliferation and apoptosis of human umbilical vein ECs were examined in the presence of exosomes.

Results Following the characterization of the isolated exosomes for their size and shape, the internalization of exosomes by ECs was visualized after 4 h. Antibody arrays showed enrichment of anti-angiogenic proteins in plasma exosomes. Interestingly, pro- and anti-angiogenic proteins (MMP-9, DPPIV, serpin F1) were elevated in HNC exosomes compared to HD exosomes. Accordingly, exosomes from early-stage HNC, NED and HD showed a stronger inhibition of EC tubulogenesis, migration and proliferation and induced more apoptosis in ECs than exosomes from late-stage HNC.

Conclusion  While in the healthy state pro- and anti-angiogenic factors of the exosomes maintain the balance, with advancing tumor stage it shifts in favor of angiogenesis stimulation. Hence, this opens up new potential therapeutic targets to reduce the risk of tumor progression in HNC.

Deutsche Forschungsgemeinschaft (DFG), Stiftung für Krebs- und Scharlachforschung der Universität Heidelberg

Publikationsverlauf

Artikel online veröffentlicht:
12. Mai 2023