Involvement of HIF-1α and GPER in hypoxia-induced tube formation. Tube formation was evaluated in HUVECs cultured for 2 h in medium collected from CAFs which were cultured under normoxia or hypoxia (2% O2 for 12 h). To this end, CAFs were transfected with control shRNA (a), shHIF-1α (b) or shGPER (c) and exposed to hypoxia, as indicated. Tube formation is rescued in HUVECs treated with 10 ng/mL VEGF and cultured in medium from CAFs transfected with shGPER and cultured under hypoxia (2% O2 for 12 h). Data are representative of three independent experiments performed in triplicate.