The Impact of Conventional and Carbon Ion Irradiation on Metastatic Potential of Tumor Cells

Abstract

AIM: There are clinical and experimental studies indicating that ionizing radiation might promote metastatic processes of malignant tumors. The mechanism of radiation-induced metastatic potential of cancer remains substantially elusive. Carbon ion irradiation may suppress metastatic potential of cancer cells. A detailed understanding of the mechanisms and molecular pathways activated in metastatic progression is crucial in identifying new treatment options for anticancer therapy that target metastasis. MATERIALS AND METHODS: The systematic review was conducted by searching for keywords in Pubmed (January 2000 - May 2014) using the search terms: ‘photon irradiation’, ‘particle irradiation’, ‘carbon ion irradiation’, ‘migration’, ‘invasion’, ‘angiogenesis’ and ‘metastasis’. RESULTS: The following strategies to counteract the ionizing radiation-induced metastasis might improve the treatment result of photon irradiation. Combining PI3K/Akt inhibitors LY294002 with ioninzing radiation might suppress radiation-induced MMP-9 mRNA expression. Inhibitors of integrin α2β1 and EGFR in combination with ionizing radiation might suppress invasiveness of lung cancer cells. The combination of inhibition of NF-κB/β1-integrin signaling with radiotherapy might suppress the invasiveness induced by ionizing radiation. Radiation therapy combined with the tyrosine kinase inhibitors (TKI) vandetanib (anti-EGFR plus anti-VEGFR) to inhibit glioblastoma growth might improve the treatment results of photon irradiation. Combining of matrix metalloproteinase inhibitor Metastat or microtubule stabilizing agent Patupilone with ionizing radiation to target radiation-induced invasion and angiogenesis might improve the efficacy of radiotherapy. The combination of radiotherapy with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) antiangiogenic agents resulted in reduced cell proliferation, migration and tube formation. Carbon ion irradiation provides both physical and biological advantages, such as the inverted dose-depth profile in tissue and an increased relative biological effectiveness (RBE) in the tumor region. In addition, carbon beam irradiation may have advantages such as inhibitory effects on metastatic potential of cancer cells, distinct from photon irradiation. CONCLUSIONS: Many studies have demonstrated that ionizing radiation can promote invasion and/or metastasis. The strategies to counteract the ionizing radiation-induced metastasis might improve the treatment results of photon irradiation. Heavy-ion irradiation may be superior to conventional photon therapy in its possible effects for the prevention of metastasis of irradiated malignant tumor cells in addition to its physical dose distribution. Further investigation to elucidate the intricate molecular mechanisms involved in metastatic progression specifically associated with photon and carbon ion irradiation is warranted.