FLT4 and head and neck squamous cell carcinoma: In contrast to the HNSCC cells, sEVs isolated from HaCaT cells cultured in hypoxic conditions showed downregulated abundance of most angiogenesis-related proteins, except integrins, angiopoietin receptor Tie-2-mediated signaling, VEGFR3 signaling in lymphatic endothelium, and TGF-β signaling-associated proteins, which were up-regulated in sEVs isolated from HaCat cells exposed to 5% O2 (Figure 6A).