Tamoxifen-resistant glioma-cell sub-populations are characterized by increased migration and proliferation

Autor: Maximilian J. A. Puchner, Alf Giese
Rok vydání: 2000
Předmět:
Zdroj: International Journal of Cancer. 86:468-473
ISSN: 1097-0215
0020-7136
DOI: 10.1002/(sici)1097-0215(20000515)86:4<468::aid-ijc4>3.0.co;2-r
Popis: 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.
Databáze: OpenAIRE
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