{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:56:04Z","timestamp":1782284164277,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Torino","award":["20174TB8KW"],"award-info":[{"award-number":["20174TB8KW"]}]},{"name":"PRIN Italian Ministry of University and Research (MUR)","award":["20174TB8KW"],"award-info":[{"award-number":["20174TB8KW"]}]},{"name":"\u201cLeveraging Basic Knowledge of the Ion Channel Network in Cancer For Innovative Therapeutic Strategies (LIONESS)","award":["20174TB8KW"],"award-info":[{"award-number":["20174TB8KW"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The tumoral microenvironment often displays peculiar features, including accumulation of extracellular ATP, hypoxia, low pH-acidosis, as well as an imbalance in zinc (Zn2+) and calcium (Ca2+). We previously reported the ability of some purinergic agonists to exert an anti-migratory activity on tumor-derived human endothelial cells (TEC) only when applied at a high concentration. They also trigger calcium signals associated with release from intracellular stores and calcium entry from the external medium. Here, we provide evidence that high concentrations of BzATP (100 \u00b5M), a potent agonist of P2X receptors, decrease migration in TEC from different tumors, but not in normal microvascular ECs (HMEC). The same agonist evokes a calcium increase in TEC from the breast and kidney, as well as in HMEC, but not in TEC from the prostate, suggesting that the intracellular pathways responsible for the P2X-induced impairment of TEC migration could vary among different tumors. The calcium signal is mainly due to a long-lasting calcium entry from outside and is strictly dependent on the presence of the receptor occupancy. Low pH, as well as high extracellular Zn2+ and Ca2+, interfere with the response, a distinctive feature typically found in some P2X purinergic receptors. This study reveals that a BzATP-sensitive pathway impairs the migration of endothelial cells from different tumors through mechanisms finely tuned by environmental factors.<\/jats:p>","DOI":"10.3390\/cancers14112743","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T03:33:18Z","timestamp":1654054398000},"page":"2743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["P2X Purinergic Receptors Are Multisensory Detectors for Micro-Environmental Stimuli That Control Migration of Tumoral Endothelium"],"prefix":"10.3390","volume":"14","author":[{"given":"Giorgia","family":"Scarpellino","sequence":"first","affiliation":[{"name":"Department of Life Sciences & Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-8389","authenticated-orcid":false,"given":"Tullio","family":"Genova","sequence":"additional","affiliation":[{"name":"Department of Life Sciences & Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0235-6102","authenticated-orcid":false,"given":"Elisa","family":"Quarta","sequence":"additional","affiliation":[{"name":"Department of Life Sciences & Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-3252","authenticated-orcid":false,"given":"Carla","family":"Distasi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Dionisi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4576-1594","authenticated-orcid":false,"given":"Alessandra","family":"Fiorio Pla","sequence":"additional","affiliation":[{"name":"Department of Life Sciences & Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-4446","authenticated-orcid":false,"given":"Luca","family":"Munaron","sequence":"additional","affiliation":[{"name":"Department of Life Sciences & Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1124\/pr.113.008029","article-title":"Purinergic Signaling and Blood Vessels in Health and Disease","volume":"66","author":"Burnstock","year":"2014","journal-title":"Pharmacol. 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