INDUCTION OF DIFFERENTIATION OF HUMAN OLFACTORY NEUROBLASTOMA-CELLS INTO ODORANT-RESPONSIVE CELLS

Olfactory neuroblastoma is a rare malignancy of the olfactory mucosa t hat may be derived from the olfactory epithelium. To characterize this tumor, we cultured olfactory neuroblastoma cells in the presence or a bsence of growth factors (transforming growth factor a and basic fibro blast growth factor) known to affect olfactory tissue and assessed the ir responsiveness to known odorants by measuring changes in intracellu lar calcium. Untreated cells did not respond to odorants. Basic fibrob last growth factor treatment had cytotoxic effects, and treated cells did not respond to odorants. Transforming growth factor a treatment re sulted in the induction of odor responsiveness in these cells. Cells r esponded to odorants at 100 nM to 100 mu M concentrations and responde d with both increases and decreases in intracellular calcium. Increase s in intracellular calcium were mediated by a calcium influx and were reversibly blocked by compounds known to inhibit second messenger path ways in olfactory receptor neurons. The calcium responses of the olfac tory neuroblastoma cells were thus specific to the odorants and simila r to those found in olfactory receptor neurons. The results support th e notion that olfactory neuroblastoma cells may be of olfactory origin and thus they can be used as a model cell line to study human olfacti on. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.