The role of protein kinase C alpha in U-87 glioma invasion

To investigate the hypothesis that protein kinase C alpha (PKC alpha) is fu nctional glial tumor cell invasion, stable PKC alpha sense and antisense tr ansfected U-87 cell lines were established and PKC alpha expression charact erized by Western blot and PKC activity assays. Invasion assays including b arrier migration (Koochekpour er ai., Extracellular matrix proteins inhibit proliferation, upregulate migration and induce morphological changes in hu man glioma lines. Eur. J. Cancel,1995, 31, 375-380; Merzak et nl., CD44 med iates human glioma cell adhesion and invasion ill vitro. Cancer Res., 1994, 54, 3988-3992; Merzak et al., Cell surface gangliosides are involved in th e control of human glioma cell invasion in vitro. Neurosci. Lett., 1994, 17 7, 11-16), and spheroid confrontation were used to study the relationship b etween PKC alpha expression and invasiveness. PKC alpha overexpressing clon es show increased barrier migration (1.5x) relative to the control transfec ted clones. PKC alpha inhibited clones exhibited reduced invasiveness, to < 50%. In coculture with PKC alpha overexpressing clones, the remaining norma l 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 i n 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 ri ghts reserved.