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.
NAADP-Dependent Ca2+ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis
Annarita Favia,Irene Pafumi,Marianna Desideri,F. Padula,C. Montesano,D. Passeri,C. Nicoletti,A. Orlandi,D. Del Bufalo,M. Sergi,E. Ziparo,F. Palombi,A. Filippini
Published 2016 in Scientific Reports
ABSTRACT
PUBLICATION RECORD
- Publication year
2016
- Venue
Scientific Reports
- Publication date
2016-01-06
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- b16 melanoma
A murine VEGF-secreting melanoma cell line used here as the in vivo and in vitro model to study NAADP-dependent signaling in tumor progression.
Aliases: B16 melanoma cells
- ca2+ signaling
Intracellular calcium release pathway controlled by NAADP, investigated here as a mechanism underlying tumor growth, angiogenesis, and metastasis.
Aliases: calcium signaling, intracellular Ca2+ release
- lung metastases
Secondary tumor deposits in the lung used in this study as an endpoint to measure metastatic dissemination of B16 melanoma cells.
Aliases: lung metastatization
- naadp
Nicotinic acid adenine dinucleotide phosphate, a second messenger that controls intracellular Ca2+ release and mediates VEGF signaling in endothelial and tumor cells.
Aliases: nicotinic acid adenine dinucleotide phosphate
- ned-19
A pharmacological inhibitor of NAADP used in this study to block NAADP-dependent Ca2+ signaling in vivo and in vitro.
- neoangiogenesis
The formation of new blood vessels within or around tumors, evaluated here by measuring tumor vascularization in the murine melanoma model.
Aliases: tumor vascularization, angiogenesis
- vegf
Vascular endothelial growth factor, a potent angiogenic factor whose signaling in endothelial and tumor cells is investigated here for NAADP dependence.
Aliases: vascular endothelial growth factor
- vegfr2
The primary receptor for VEGF expressed on endothelial and tumor cells, whose expression in B16 cells is modulated by Ned-19 treatment.
Aliases: vascular endothelial growth factor receptor 2
REFERENCES
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