The role of protein kinase Calpha in U-87 glioma invasion.
To investigate the hypothesis that protein kinase Calpha (PKCalpha) is functional glial tumor cell invasion, stable PKCalpha sense and antisense transfected U-87 cell lines were established and PKCalpha expression characterized by Western blot and PKC activity assays. Invasion assays including barrier migration (Koochekpour et al., Extracellular matrix proteins inhibit proliferation, upregulate migration and induce morphological changes in human glioma lines. Eur. J. Cancer, 1995, 31, 375-380; Merzak et al., 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 PKCalpha expression and invasiveness. PKCalpha overexpressing clones show increased barrier migration (1.5x) relative to the control transfected clones. PKCalpha inhibited clones exhibited reduced invasiveness, to < 50%. In coculture with PKCalpha overexpressing clones, the remaining normal fetal rat brain aggregate volume was significantly decreased (up to 200%) but 90% of the initial brain volume was left in PKCalpha inhibited clone in the rat brain aggregate tumor spheroid confrontation. This effect was not associated with significant growth inhibition. We conclude that expression of PKCalpha in glioma-derived cell lines appears to be central to glioma invasion in vitro.
Cho
K K
KK
Department of Neurosurgery, Henry Ford Hospital, Detroit, MI 48202, USA.
Mikkelsen
T
T
Lee
Y J
YJ
Jiang
F
F
Chopp
M
M
Rosenblum
M L
ML
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D003094:Collagen; D016373:DNA, Antisense; D018076:DNA, Complementary / Q000235:genetics; D004338:Drug Combinations; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D007797:Laminin; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha; D011509:Proteoglycans; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D018076:DNA, Complementary; D004338:Drug Combinations; D007527:Isoenzymes; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha