Cell scattering and migration induced by autocrine transforming growth factor α in human glioma cells in vitro

• Published in: Cancer research (Chicago, Ill.) Vol. 57; no. 24; pp. 5598 - 5604
• Main Authors: EL-OBEID, A, BONGCAM-RUDLOFF, E, SÖRBY, M, ÖSTMAN, A, NISTER, M, WESTERMARK, B
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.1997
• Subjects: Antibodies, Monoclonal - pharmacology; Biological and medical sciences; Blotting, Northern; Cell Movement - physiology; Enzyme-Linked Immunosorbent Assay; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Ligands; Medical sciences; Neurology; Phosphorylation; Precipitin Tests; Receptor, Epidermal Growth Factor - immunology; Receptor, Epidermal Growth Factor - metabolism; Receptor, Epidermal Growth Factor - physiology; RNA, Messenger - metabolism; Transfection; Transforming Growth Factor alpha - biosynthesis; Transforming Growth Factor alpha - genetics; Transforming Growth Factor alpha - physiology; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses; Tyrosine - metabolism; Human; Nervous system diseases; Enzyme; Transferases; Migration; Malignant tumor; Gene expression; In vitro; Malignant glioma; Autocrine secretion; Epidermal growth factor; Kinase; Central nervous system disease; Established cell line; Tumor progression; Transforming growth factor α; Tumor cell; Biological receptor
• ISSN: 0008-5472; 1538-7445

In the present investigation, we have transfected a human malignant glioma cell line, U-1242 MG, and derived clones that produce transforming growth factor alpha (TGF-alpha) in an inducible manner using the tetracycline suppressible vector system. TGF-alpha 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-alpha. 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.