Multifocal tumor recurrence of glioblastomas occurs in up to 14% of patients. In 
a parallel phase-II-study investigating post-operative treatment with tamoxifen 
(TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients 
(33%) showed multifocal recurrence, which developed after a mean of 46 weeks, 
raising the question of an association with therapy. We studied the 
interrelation of proliferation and migration in the presence of different 
protein-kinase-C(PKC) inhibitors (TAM, staurosporine, hypericin) in 2 glioma 
cell lines. In addition, 3 cell lines were selected for TAM resistance by 
repeated cycles of treatment with sub-lethal concentrations of TAM. The 
proliferative capacity and the invasive potential of selected sub-populations 
were assessed using growth-curve experiments, monolayer migration, and 
cell-adhesion assays. Treatment with all PKC inhibitors tested resulted in a 
dose-dependent decrease of proliferation, while motility was altered only at 
significantly higher doses. Resistance to TAM occurred in all 3 selected cell 
lines. The TAM-resistant sub-populations showed significantly increased 
proliferation, migration and adhesion as compared with the parental 
(non-selected) cell line. The higher incidence of multifocal disease after TAM 
treatment was paralleled by increased migratory potential of TAM-treated cells 
in vitro.