Characterization of dose-dependent metabolic changes in melanoma cells after irradiation in vitro and in vivo


Characterization of dose-dependent metabolic changes in melanoma cells after irradiation in vitro and in vivo

Mosch, B.; Müller, K.; Pietzsch, J.

Background:

Although irradiation is a powerful tool for the therapy of solid tumors, single cells often elude this treatment and constitute a basis for recurrence of the primary tumor and formation of metastases. This rises the question if irradiation-dependent metabolic changes could be responsible for a predisposition of certain cells to show enhanced survival and migratory activity. The aim of our study was to investigate metabolic properties of irradiated melanoma cells and thus to develop and validate appropriate in vitro and in vivo models to characterize new radiopharmaceuticals for diagnosis and therapy of metastases and solid tumors.

Materials and methods:

We applied different single-dose X-ray irradiation (1, 2, 5, 7, 10, and 20 Gy) to murine B16-F10 melanoma cells. At particular times we analyzed cell viability, growth properties, clonogenic regrowth capability, cellular proliferation, and expression of cell cycle markers. Furthermore, we analyzed the cellular uptake of the radiotracers 2-[18F]Fluor-2-desoxy-D-glucose and 3-O-Methyl-[18F]fluor-L-DOPA, providing information about the glucose and amino acid metabolism before and after irradiation. Additionally, we performed in vivo studies in a syngeneic mouse model to analyze the capability of untreated and irradiated cells to form lung metastases.

Results:

In a dose-dependent manner we detected a decrease in the viability, growth properties and tracer uptake of the melanoma cells. These findings appeared particularly in the period 3 to 6 days after irradiation. In contrast, already one day after irradiation cell cycle analyses showed an increase in the number of G2/M phase cells and the expression of G2-phase markers in irradiated compared to untreated cells. Further we demonstrated an influence of irradiation according to the ability to form lung metastases in the mouse.

Conclusions:

Our results indicate that the combination of different in vitro and in vivo approaches is useful for a detailed characterization of metabolic changes in melanoma cells after irradiation. Additionally, the presented approach gives information about dose-dependent effects. These models enable us to characterize new radiotracers and furthermore, to investigate metabolic effects of applied radiopharmaceuticals in combination with experimental radiation therapy.

  • Poster
    20th Meeting of the European Association for Cancer Research, 05.-08.07.2008, Lyon, France
  • Abstract in refereed journal
    EJC Supplements 6(2008)9, 129

Permalink: https://www.hzdr.de/publications/Publ-11121
Publ.-Id: 11121