Placental growth factor (PIGF) is produced by tumor cells and stimulates tumor growth and metastasis in part by upregulation of hypoxia inducible factor HIF1 alpha. Orchestration of tumor cell proliferation and migration involves oscillations of cytosolic Ca2+ activity ([Ca2+](i)). The [Ca2+](i) oscillations could be accomplished by triggering of intracellular Ca2+ release followed by store-operated Ca2+-entry (SOCE). Mechanisms accomplishing SOCE include the pore-forming ion channel unit Orail and its regulator STIM1. The present study explored whether P1GF influences the expression of Orail and STIM1, as well as SOCE and whether this effect impacts on HIF1 alpha expression. To this end, ovary carcinoma cells were cultured for 24 h without and with PIGF (10 ng/ml). Orail, STIM1 and HIF1 alpha transcript levels were quantified utilizing RT-PCR and Orail, STIM1 and HIF1 alpha protein levels by Western blotting. [Ca2+]; was estimated from Fura-2-fluorescence and SOCE from increase of [Ca2+](i) following Ca2+ re-addition after Ca2+-store depletion with extracellular Ca2+ removal and sarcoendoplasmatic Ca2+-ATPase (SERCA) inhibitor thapsigargin (1 mu M). As a result, exposure of ovary carcinoma cells to PIGF was followed by a significant increase of Orail as well as STIM1 transcript and protein levels. PIGF significantly increased store-operated Ca2+-entry following re-addition of extracellular Ca2+, an effect virtually abrogated by Orai1 inhibitor MRS1845 (10 mu M). PIGF further increased HIF1 alpha transcript and protein levels, an effect again significantly blunted by MRS1845 (10 mu M). In conclusion, PlGF upregulates expression of both, Orail and STIM1 thus enhancing store-operated Ca2+-entry with subsequent upregulation of HIF1 alpha. (C) 2019 Elsevier Inc. All rights reserved.