title: The influence of neuropilin-1 silencing on semaphorin 3A and 3C activity in B16(F10) murine melanoma cells.
abstract: Neuropilin-1 (Nrp1), originally characterized as an adhesion molecule in the nervous system, is a co-receptor for class-3 semaphorins. Neuropilins and semaphorins are highly expressed in a wide spectrum of tumors and have been shown to influence their growth and vascularization. Despite the growing body of data on neuropilin/semaphorin regulation of tumor growth, still the exact mechanism of their activity remains to be elucidated. Previously published data suggests that Nrp1 has both anti- and promigratory characteristics in different tumor types, although no data is available on its role in melanoma cells. In this paper, we studied the effect of Nrp1 downregulation on B16(F10) melanoma cells migration. Our results show that the silencing of Nrp1 significantly increases the overall mobility of B16(F10) cells and changes their morphology. Moreover, Nrp1-silenced B16(F10) cells show a decreased response to Sema3A. We also observed reduced binding of Sema3A to these cells. Contrarily, no changes were observed in the binding of Sema3C to Nrp1-silenced B16(F10) cells, nor in its chemorepellent activity. Our results suggest that modulation of B16(F10) cells migratory ability by semaphorin 3A can be preferentially mediated by Nrp1, while the contribution of semaphorin 3C in this process is less evident. In addition, silencing of Nrp1 did not change the migratory ability of B16(F10) cells towards VEGF.
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland. amazurek@io.gliwice.pl
authors.forename: A M
authors.initials: AM
authors.lastname: Mazurek
authors.forename: M
authors.initials: M
authors.lastname: Olbryt
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D048430:Cell Shape; D017077:Culture Media, Conditioned / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology*; D040121:Semaphorin-3A / Q000502:physiology*; D039961:Semaphorins / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; D039961:Semaphorins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C510203:semaphorin 3C protein, mouse; D039942:Neuropilin-1