bFGF induces differentiation and death of olfactory neuroblastoma cells.
Olfactory neuroblastoma (ONB) is a highly vascularized and malignant tumor arising in olfactory neuronal precursors from the paranasal sinuses. Previously, we showed that treatment of JFEN cells with transforming growth factor (TGF)-alpha caused them to differentiate and respond to chemical odorants, whereas basic fibroblast growth factor (bFGF) treated cells differentiated and died. In the present study we show that established ONB tumors treated with bFGF upregulate the bFGF receptor (FGFR1) prior to differentiation. This cellular differentiation was evidenced by bFGF-induced expression of the human runt homologue AML1 (PEBP2 alpha B, CBFA-2) that is highly expressed in developing olfactory neuroepithelium and TrkA, a preferred nerve growth factor receptor. Since TrkA is expressed in supporting cells, but not in mature olfactory neurons, we hypothesize that the expression of AML1 and TrkA in bFGF-treated JFEN cells induced supporting cell differentiation. Collectively, these results have implications for the treatment of patients afflicted with ONB.
Nibu
K
K
Department of Otolaryngology-Head and Neck Surgery, Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Li
G
G
Kaga
K
K
Rothstein
J L
JL
D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009447:Neuroblastoma / Q000473:pathology*; D009833:Olfactory Pathways / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D020917:Receptor, trkA / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D017931:DNA Primers; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D020917:Receptor, trkA