Artikel
Inducible expression of p57KIP2
inhibits glioma cell motility and invasion
Die induzierbare p57KIP2
Expression hemmt die Zellmotilität und -invasion von Gliomzellen
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
Text
Objective
It has been hypothesized that migration and proliferation are mutually exclusive cellular programs in invasive gliomas. Previous results indicated that p57KIP2 overexpression, a cyclin-dependent kinase inhibitor (CDKI), significantly decreases cellular proliferation and promotes cell senescence in malignant glioma cell lines. The purpose of the present study was to focus on the migratory and invasive potential of malignant glioma cells under the influence of p57KIP2 expression, and to determine whether the above described dichotomous cellular behaviour holds for glioma cells expressing this CDKI.
Methods
Inducible stably transfected p57KIP2 expressing U373 and U87 glioma cell lines were used (in a tetracycline repressor system) to investigate differences in cell migration behaviour in a phagokinetic track assay on gold particles. Effects of extracellular matix (ECM) on U373 was determined in p57+ and p57- cells on surfaces coated with fibronectin, laminin, type I and IV collagens. Then the invasion of these cells across BD Biocoat Matrigel invasion chambers was determined.
Results
U373 motility was significantly reduced after p57KIP2 induction, and was not altered by different ECM proteins. The invasion chamber assay showed that p57+ cells exhibited a 35% reduction in their invasive capacity as compared to p57- cells.
Conclusions
Inducible expression of p57KIP2 in cell lines deficient in this CDKI reduces their motility and invasiveness. These results taken together with our previous ones demonstrate that p57KIP2 overexpression simultaneously downregulates proliferation and migration, which is in contrast to the initial hypothesis.
Forschungsstipendium der Deutschen Forschungsgemeinschaft (Pe 758/2-1)