Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2

Primitive neuroectodermal tumours (PNET) are thought to derive from the malignant transformation of pluripotent CNS precursors although this hypothesis has yet to be tested in vitro. Here we show that cells of a human PNET cell line 'Dev' express functional fibroblast growth factor (FGF) receptors (FGFR) and respond to FGF2 as multipotent CNS precursors. FGF2 induces tyrosine phosphorylation of FGFR-1 and FGFR-2 and many cellular substrates including MAP kinases and stimulates proliferation. Cells detach from plastic substrates and proliferate to form large clusters of undifferentiated cells. After adhesion to polylysine, cells migrate out from the clusters and differentiate. The majority of differentiated cells express neuronal phenotypes but distinct subpopulations express oligodendrocytic and astrocytic markers. Mature neural differentiation markers are not otherwise detected in Dev cells in defined medium. Identical results were obtained with 12 monoclonal subclones as well as the parent cell line, confirming that Dev cells are multipotent. This extends evidence that multipotent CNS precursors are the cellular substrate from which certain PNET develop and shows that FGF2 is a potent proliferation and differentiation inducer for PNET cells in vitro, suggesting that FGF2 may also modulate the evolution of PNET in vivo. Finally our results suggest that PNET cell lines may provide models to elucidate the biology of human multipotent CNS precursors.