Meta-iodobenzylguanidine (mIBG) uptake and storage in the human neuroblastoma cell line SK-N-BE(2C).
Whilst many human neuroblastoma cell lines have been studied to see if they are capable of taking up mIBG, few appear to have this ability. This contrasts markedly to the situation in vivo, where uptake has been demonstrated in the majority of tumours investigated. Here we report on the human neuroblastoma cell line SK-N-BE(2C) and demonstrate that mIBG uptake can occur in this cell line through 2 mechanisms. At low concentrations of mIBG (approximately 10(-8) M) an active transport process predominates, whereas at non-physiological levels (10(-4) M) uptake occurs through passive diffusion. The active transport process is ATP-, Na(+)- and temperature-dependent. Uptake is blocked by 10(-6) M desipramine, an inhibitor of the uptake-I mechanism involved in amine transport. In contrast, desipramine has no effect on the passive diffusion of mIBG into cells. The active transport mechanism for mIBG uptake appears rather promiscuous for biogenic amines, as dopamine, tyramine and nor-adrenaline were highly efficient at blocking mIBG entry to the cell. Serotonin and histamine were capable of interfering with mIBG uptake only at much higher concentrations. Electron microscopy of SK-N-BE(2C) cells revealed a paucity of neurosecretory granules. Biochemical investigations demonstrated the majority of mIBG to be present in the cytoplasm of cells. The availability of a human neuroblastoma cell line that grows well, both as xenograft and in culture, should further our understanding of the cytotoxic effects of mIBG and thus enhance its clinical usefulness.
Lashford
L S
LS
Imperial Cancer Research Fund, Frenchay Hospital, Bristol, UK.
Hancock
J P
JP
Kemshead
J T
JT
D019797:3-Iodobenzylguanidine; D000970:Antineoplastic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D001693:Biological Transport, Active; D002460:Cell Line; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D009447:Neuroblastoma / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D000970:Antineoplastic Agents; D007462:Iodobenzenes; D012701:Serotonin; D019797:3-Iodobenzylguanidine; D006632:Histamine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine