El-Obeid A, Bongcam-Rudloff E, Sörby M, Ostman A, Nistér M, Westermark B
Department of Pathology, Uppsala University, University Hospital, Sweden.
Cancer Res. 1997 Dec 15;57(24):5598-604.
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.
在本研究中，我们转染了一种人恶性胶质瘤细胞系U-1242 MG，并使用四环素可抑制载体系统获得了以可诱导方式产生转化生长因子α（TGF-α）的克隆。通过Northern分析、ELISA以及对代谢标记细胞的免疫沉淀法证实了TGF-α的表达。诱导蛋白的功能活性通过在诱导TGF-α时发现表皮生长因子受体（EGFR）酪氨酸磷酸化得到证明。证实了对细胞运动性有明显影响，即细胞散射以及单个胶质瘤细胞的吞噬运动轨迹面积增加。EGFR酪氨酸激酶激活与细胞密度无关这一事实表明，EGFR激酶的自分泌激活发生在单细胞水平。这些发现很有意义，因为细胞运动性增加很可能是体内胶质瘤细胞侵袭的一个必要条件。结果表明，由于EGFR及其配体的共表达，单个胶质瘤细胞能够作为独立的自分泌运动单位发挥作用。
