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Neural cell surface differentiation antigen gp130^RB13-6 induces fibroblasts and glioma cells to express astroglial proteins and invasive properties

^a Institute of Cell Biology (Cancer Research), University of Essen Medical School, D-45122 Essen, Germany; and

^b Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, University Hospital, 3-9000 Ghent, Belgium

Transient expression of the differentiation and tumor cell surface antigen gp130^RB13-6 characterizes a subset of rat glial progenitor cells susceptible to ethylnitrosourea-induced neurooncogenesis. gp130^RB13-6 is as a member of an emerging protein family of ecto-phosphodiesterases/nucleotide pyrophosphatases that includes PC-1 and the tumor cell motility factor autotaxin. We have investigated the potential role of gp130^RB13-6 in glial differentiation by transfection of three cell lines of different origin that do not express endogenous gp130^RB13-6 (NIH-3T3 mouse fibroblasts; C6 and BT7Ca rat glioma cells) with the cDNA encoding gp130^RB13-6. The effect of gp130^RB13-6 expression was analyzed in terms of overall cell morphology, the expression of glial cell-specific marker proteins, and invasiveness. Transfectant sublines, consisting of 100% gp130^RB13-6-positive cells, exhibited an altered, bipolar morphology. Fascicular aggregates of fibroblastoid cells subsequently developed into mesh-like patterns. Contrary to the parental NIH-3T3 and BT7Ca cells, the transfectant cells invaded into collagen type I. As shown by immunofluorescence staining of the transfectant sublines as well as of primary cultures composed of gp130^RB13-6-positive and -negative cells, expression of gp130^RB13-6 induced coexpression of proteins typical for glial cells and their precursors, i.e., glial fibrillary acidic protein, the low affinity nerve growth factor receptor, and the neural proteins Thy-1, Ran-2, and S-100. In accordance with its expression in the immature rat nervous system, gp130^RB13-6 may thus have a significant role in the glial differentiation program and its subversion in neurooncogenesis.—Deissler, H., Blass-Kampmann, S., Bruyneel, E., Mareel, M., Rajewsky, M. F. Neural cell surface differentiation antigen gp130^RB13-6 induces fibroblasts and glioma cells to express astroglial proteins and invasive properties.

Key Words: glial cells • astrocytes • GFAP • invasion • neurooncogenesis

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