Up-regulation of vimentin expression in low-density malignant glioma cells as immediate and late effects under irradiation and temozolomide treatment.
Nervous system tumors are one of the leading causes of cancer related death. Specific mechanisms facilitating the invasive behavior of gliomas remain obscure. Advanced simulation models of the in vivo response to therapy conditions should potentially improve malignant glioma treatment. Expressional profiling of vimentin--one of reliable pro-invasive tumor makers--in those simulation models was the goal of this study, in order to estimate a pro-invasive response of surviving malignant glioma cells under clinically relevant therapeutic conditions. Human U87-MG malignant glioma cells were used. These cells are characterized by the wild p53-phenotype, which is relevant for the majority of primary malignant glioblastomas. Experimental design foresaw the cells to undergo either irradiation or chemo-treatment with temozolomide alone, or combined treatment. Expression profiling of vimentin was performed by quantitative "Real-Time"-PCR under all treatment conditions simulating diverse tumor regions. Here we demonstrated that vimentin expression patterns in human malignant glioma cells strongly depend on cellular density, algorithms of drug delivery and chemo/radio treatment. Substantial differences were recognized between immediate and late therapy effects. Significant increase in vimentin expression levels was detected particularly in low-density cell cultures under durable treatment with constant concentration levels of temezolomide. Simulation of variable intratumoral regional conditions (central intratumoral regions vs. disseminated malignant cells in peripheral regions) demonstrated differential response of vimentin expression in malignant glioma cell cultures treated under clinically relevant conditions. Slight ebbing of expression levels as late effects of the treatment in confluent cultures may correspond to necrotic processes clinically observed in central intratumoral regions. Contrary, in disseminated malignant cells of peripheral regions therapy resulted in vimentin-inducing effects. This is in agreement with the clinical observations of an increased aggressiveness and malignancy grade of post-operatively chemo/radio-treated malignant gliomas.
Department of Radiology, Friedrich-Wilhelms-University of Bonn, 53105 Bonn, Germany.
Daniela
D
Trog
Kristina
K
Yeghiazaryan
Hans H
HH
Schild
Olga
O
Golubnitschaja
D000465:Algorithms; D002452:Cell Count; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D012313:RNA / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays
D014746:Vimentin; D012313:RNA