文章基本信息

标题：NAADP-Dependent Ca²⁺ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis
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作者：Annarita Favia ; Irene Pafumi ; Marianna Desideri 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
DOI：10.1038/srep18925
出版社：Springer Nature
摘要：A novel transduction pathway for the powerful angiogenic factor VEGF has been recently shown in endothelial cells to operate through NAADP-controlled intracellular release of Ca²⁺. In the present report the possible involvement of NAADP-controlled Ca²⁺ signaling in tumor vascularization, growth and metastatic dissemination was investigated in a murine model of VEGF-secreting melanoma. Mice implanted with B16 melanoma cells were treated with NAADP inhibitor Ned-19 every second day for 4 weeks and tumor growth, vascularization and metastatization were evaluated. Control specimens developed well vascularized tumors and lung metastases, whereas in Ned-19-treated mice tumor growth and vascularization as well as lung metastases were strongly inhibited. In vitro experiments showed that Ned-19 treatment controls the growth of B16 cells in vitro , their migratory ability, adhesive properties and VEGFR2 expression, indicating NAADP involvement in intercellular autocrine signaling. To this regard, Ca²⁺ imaging experiments showed that the response of B16 cells to VEGF stimulation is NAADP-dependent. The whole of these observations indicate that NAADP-controlled Ca²⁺ signaling can be relevant not only for neoangiogenesis but also for direct control of tumor cells.