NAADP-Dependent Ca2+ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis

Annarita Favia, Irene Pafumi, Marianna Desideri, Fabrizio Padula, Camilla Montesano, Daniela Passeri, Carmine Nicoletti, Augusto Orlandi, Donatella Del Bufalo, Manuel Sergi, Elio Ziparo, Fioretta Palombi, Antonio Filippini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number18925
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jan 6 2016

ASJC Scopus subject areas

  • General

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