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01.12.2018 | Primary research | Ausgabe 1/2018 Open Access

Cancer Cell International 1/2018

Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts

Zeitschrift:
Cancer Cell International > Ausgabe 1/2018
Autoren:
Henry Oppermann, Johannes Dietterle, Katharina Purcz, Markus Morawski, Christian Eisenlöffel, Wolf Müller, Jürgen Meixensberger, Frank Gaunitz
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12935-018-0611-2) contains supplementary material, which is available to authorized users.
Henry Oppermann and Johannes Dietterle contributed equally to this work

Abstract

Background

Glioblastoma (GBM) is a tumor of the central nervous system. After surgical removal and standard therapy, recurrence of tumors is observed within 6–9 months because of the high migratory behavior and the infiltrative growth of cells. Here, we investigated whether carnosine (β-alanine-l-histidine), which has an inhibitory effect on glioblastoma proliferation, may on the opposite promote invasion as proposed by the so-called “go-or-grow concept”.

Methods

Cell viability of nine patient derived primary (isocitrate dehydrogenase wildtype; IDH1R132H non mutant) glioblastoma cell cultures and of eleven patient derived fibroblast cultures was determined by measuring ATP in cell lysates and dehydrogenase activity after incubation with 0, 50 or 75 mM carnosine for 48 h. Using the glioblastoma cell line T98G, patient derived glioblastoma cells and fibroblasts, a co-culture model was developed using 12 well plates and cloning rings, placing glioblastoma cells inside and fibroblasts outside the ring. After cultivation in the presence of carnosine, the number of colonies and the size of the tumor cell occupied area were determined.

Results

In 48 h single cultures of fibroblasts and tumor cells, 50 and 75 mM carnosine reduced ATP in cell lysates and dehydrogenase activity when compared to the corresponding untreated control cells. Co-culture experiments revealed that after 4 week exposure to carnosine the number of T98G tumor cell colonies within the fibroblast layer and the area occupied by tumor cells was reduced with increasing concentrations of carnosine. Although primary cultured tumor cells did not form colonies in the absence of carnosine, they were eliminated from the co-culture by cell death and did not build colonies under the influence of carnosine, whereas fibroblasts survived and were healthy.

Conclusions

Our results demonstrate that the anti-proliferative effect of carnosine is not accompanied by an induction of cell migration. Instead, the dipeptide is able to prevent colony formation and selectively eliminates tumor cells in a co-culture with fibroblasts.
Zusatzmaterial
Additional file 1: Table S1. Patients and patient derived cell cultures.
Additional file 2. Setup of ring-cultures.
Literatur
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