The role of protein kinase Cα in U-87 glioma invasion

To investigate the hypothesis that protein kinase C alpha (PKC alpha) is functional glial tumor cell invasion, stable PKC alpha sense and antisense transfected U-87 cell lines were established and PKC alpha expression characterized by Western blot and PKC activity assays. Invasion assays including barrier migration (Koochekpour er ai.. Extracellular matrix proteins inhibit proliferation, upregulate migration and induce morphological changes in human glioma lines. Eur. J. Cancel,1995, 31, 375-380; Merzak et nl., CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res., 1994, 54, 3988-3992; Merzak et al., Cell surface gangliosides are involved in the control of human glioma cell invasion in vitro. Neurosci. Lett., 1994, 177, 11-16), and spheroid confrontation were used to study the relationship between PKC alpha expression and invasiveness. PKC alpha overexpressing clones show increased barrier migration (1.5x) relative to the control transfected clones. PKC alpha inhibited clones exhibited reduced invasiveness, to <50%. In coculture with PKC alpha overexpressing clones, the remaining normal fetal rat brain aggregate volume was significantly decreased (up to 20%) but 90% of the initial brain volume was left in PKC alpha inhibited clone in the rat brain aggregate tumor spheroid confrontation. This effect was not associated with significant growth inhibition. We conclude that expression of PKC alpha in glioma-derived cell lines appears to be central to glioma invasion in vitro. (C) 1999 ISDN. Published by Elsevier Science Ltd. All rights reserved.