Irradiation-induced changes in metabolism and metastatic properties of melanoma cells

As it is known that irradiation can influence cellular metabolism it is conceivable that it can induce metabolic changes which lead to a predisposition of certain cells to show enhanced survival, migratory activity and metastasis. The aim of this study was to investigate short term and long term irradiation effects on proliferation and metabolism of melanoma cells in vitro and their ability to form metastases in vivo.
B16-F10 melanoma cells were irradiated with different doses of X-ray irradiation in the range of 1 to 20 Gy. One, two, and three days (short term effects) and, furthermore, 7, 14 and 21 days (long term effects) after treatment cells were analyzed concerning cell growth, proliferation, viability, glucose and amino acid transport. Additionally, we performed in vivo studies in a syngeneic mouse model to analyze the capability of irradiated melanoma cells to form lung metastases.
The analysis of short term effects showed decreased cell growth, viability and arrest in the G2/M phase of the cell cycle while glucose transport is increased. Long term effects involve recovered proliferation, accompanied by increased glucose transport and decreased viability and amino acid transport. In vivo studies showed loss of metastasis immediately after irradiation and reduced metastasis if cells were allowed to recover proliferation before injection.
We conclude that melanoma cells as short term response to irradiation show cell cycle arrest and impairment in growth and viability. Three days after irradiation compensatory mechanisms start, leading to recovered growth within three weeks. Studies concerning metabolic properties indicate that a subpopulation of surviving melanoma cells compensate for the initial irradiation-induced damage possibly by metabolic modulations such as increase in glycolysis. As metastasis in vivo is impaired beyond recovered cell proliferation, the role of adjusted cell metabolism and additional extrinsic factors is strongly suggested.