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Cell Scattering and Migration Induced by Autocrine Transforming Growth Factor in Human Glioma Cells in Vitro¹

Department of Pathology, Uppsala University, University Hospital, S-751 85 Uppsala [A. E-O., E. B-R., M. N., B. W.], and Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S-751 24 Uppsala [M. S., A. O.], Sweden

In the present investigation, we have transfected a human malignant glioma cell line, U-1242 MG, and derived clones that produce transforming growth factor (TGF-) in an inducible manner using the tetracycline suppressible vector system. TGF- expression was confirmed by Northern analysis, by ELISA, and by immunoprecipitation of metabolically labeled cells. The functional activity of the induced protein was proven by the finding of epidermal growth factor receptor (EGFR) tyrosine phosphorylation on induction of TGF-. A clear effect on cell motility, i.e., cell scattering and an increased phagokinetic track area of individual glioma cells, was demonstrated. The fact that the EGFR tyrosine kinase activation was independent of cell density suggests that autocrine activation of the EGFR kinase occurred at the single-cell level. These findings are of interest, because increased cell motility is most likely a requirement for glioma cell invasion in vivo. The results imply that as a result of coexpression of EGFR and its ligand, individual glioma cells are capable of acting as independent autocrine locomotory units.

¹ Supported by grants from the Swedish Cancer Society.

² To whom requests for reprints should be addressed. Phone: 46-18-663821; Fax: 46-18-558931; E-mail: Bengt.Westermark@patologi.uu.se.

Received 7/ 8/97. Accepted 10/14/97.

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