Biochemical properties of monoamine-rich human neuroblastoma cells.
The biochemical, pharmacological and immunological characterization of cells derived from human neuroblastoma tumors recently acquired great interest, since these cells may be a putative donor source for transplantation in animal models of neurological disorders. We measured monoamine levels, tyrosine hydroxylase (TH) immunostaining, and the expression of major histocompatibility cell surface antigens (MHC) in 7 human neuroblastoma cell lines. Three cell lines (LAN5, NB69 and CHP126) had high levels of monoamines. TH immunostaining was strongly positive in CHP126 and LAN5, and NB69. MHC were not detected in any of the cells with high catecholamine levels. Treatment with neuroleptics increased the metabolism of dopamine in LAN5 but not in NB69. The implantation of LAN5 cells in immunocompetent, unilaterally 6-hydroxydopamine-lesioned rats decreased the apomorphine-induced contralateral rotation. The effect of the implant was greatest in animals in which LAN5 neuroblastoma cells, pretreated with dibutyryl cyclic adenosine monophosphate (DBcAMP) and prostaglandin E1 (PGE1, were implanted into the cerebral ventricle ipsilateral to the lesion, and then irrigated with DBcAMP administered through a totally implanted drug delivery system. The effect of the implant decreased after the second week. Neuroblastoma cells were found in approximately 50% of the implanted animals. TH immunostaining was weak or absent in the grafted animals. Inflammatory changes were present in the majority of the brains examined. Extensive tumor growth was present in one animal implanted with untreated cells. Grafting of cells treated with DBcAMP and PGE1 plus with mitomycin C and bromodeoxyuridine in animals immunosuppressed with cyclosporin A reduced the apomorphine-induced rotation to 40-60% of baseline levels and this reduction persisted beyond the period of infusion with DBcAMP. Intraventricular infusion of DBcAMP in animals injected with cell culture medium produced a transient reduction of rotation to 70% of baseline. The amphetamine-induced rotation was not significantly reduced during the 4 weeks follow up. Atypical cells, consistent with surviving neuroblastoma cells, were observed in the brain of all transplanted animals. TH immunostaining was weak or negative in most cases. Human neuroblastoma cells may be an alternative donor tissue for the study of the effects of transplantation in animal models of Parkinson's disease.
Mena
M A
MA
Parkinson's Disease Laboratories, New York, NY 10032.
Garcia de Yebenes
J
J
Dwork
A
A
Fahn
S
S
Latov
N
N
Herbert
J
J
Flaster
E
E
Slonim
D
D
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D006892:Hydroxydopamines; D008297:Male; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D006680:HLA Antigens; D006892:Hydroxydopamines; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine; D009638:Norepinephrine