Abstract
The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.
Highlights
The transforming growth factor-p(TGF-p) superfam- activin-B); Mullerian inhibiting substance;and the dppNg-reily plays a rolein embryogenesis and regenerationW . e lated subfamily (decapentaplegic complex and Vgr/6OA have reported that osteogenic protein-1 (OP-1) promforotmes Drosophila melanogasterV, g-1 fromxenopus laevis, Vgr-1 cell aggregation and induces the expression of the neua-nd GDF-1 from mouse, osteogenic proteins-1 and 2, the bone ral cell adhesion moleculNes-CAM and L1 in proliferat- morphogenetic proteins (BMPs) 1through 7, and dorsalin-1). ing neuroblastomax glioma hybrid NG108-15cells
Morphogenetic Activity of the BMPs in NG108-15 Cells-We showed previously that human OP-1 (hOP-1) induces the expression of the immunoglobulin superfamily cell adhesion molecules (IgCAM)
N-CAM and L1 in dividing NG108-15 cells, leading to a concentration-dependent increase in the percentage of cells pre- experiments suggest that thme orphoregulatory activityof sent in adherent clusters and epithelioid sheets [10, 19]
Summary
(Received for publication, August 2, 1993, and inrevised form, September 3, 1993). George PeridesSg, RebeccaM. Deed, the neural cell adhesion molecule N-CAM is induced by Theadditionofserum to cells growing in serum-free TGF-P in 3T3 fibroblasts(l2),byactivinindevelopinglimb medium caused a concentration-dependent increase in buds [13] and by OP-1 (BMP-7) in neuroblastoma x glioma N-CAM and L1 expression; serum did not po- NGlO8-15 hybrid cells [10]. These observations imply that a tentiate the induction of N-CAM and L1 by ng/ml distinct signaling pathway may couplethe TGF-P superfamily. The abbreviations used are: TGF-p, transforming growth factor-p; BMPb, one morphogenetic proteins; d p p , decapentaplegic complex; EGF, epidermal growth factor; FGF, fibroblast growth factor; hOP-1, recombinant human osteogenic protein-1; IgCAM, immunoglobulin superfamily cell adhesion molecule; mAb, monoclonal antibody; N-CAM, neural cell adhesion molecule; NGF, nerve growth factor; PBS, phosphate-buffered saline; ELISA,enzyme-linked immunosorbent assay
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