Abstract
Precise characterization of tumor recurrence and regrowth after radiotherapy are important for prognostic understanding of the therapeutic effect. Here, we established a novel in vivo mouse model for evaluating the characteristics of regrown tumor after repeated photon and carbon ion (C-ion) irradiations. The results showed that tumor growth rate, lung metastasis, shortening of the survival of the tumor-bearing mice, and tumor microvessel formation were promoted 2- to 3-fold, and expression of angiogenic and metastatic genes increased 1.5- to 15-fold in regrown tumors after repeated photon irradiations, whereas repeated C-ion irradiations did not alter these characteristics. Interestingly, both repeated photon and C-ion irradiations did not generate radioresistance, which is generally acquired for in vitro treatment. Our results demonstrated that the repetition of photon, and not C-ion, irradiations in vivo alter the characteristics of the regrown tumor, making it more aggressive without acquisition of radioresistance.
Highlights
With the development of current irradiation techniques, it is possible to deliver higher radiation dose into local tumor
We showed that the repeated photon irradiations promoted aggressiveness represented by the enhancement of tumor growth, metastatic potential, and increase in the number of tumor vessels in the regrown tumor (Figs 1–5)
The repeated carbon ion (C-ion) irradiations, the single fractioned dose of which is biologically equivalent to that of the photon irradiation, did not contribute to the aggressiveness and only slightly influenced the gene expression. These results indicated that the impact of repeated photon irradiations on phenotypic change and gene expression, which are closely related with tumor aggressiveness, is different from that of C-ion irradiation
Summary
With the development of current irradiation techniques, it is possible to deliver higher radiation dose into local tumor. The ionization of the C-ion reaches a maximum at the end of the beam path, and steeply drops sparing tissues beyond the tumor location This is known as the Bragg peak, and the peak can be precisely determined to occur at the tumor site for an ideal dose distribution. We previously elucidated that repetitive photon irradiations in vitro conferred significant photon and C-ion resistance in cancer cells[14,15] Since these phenotypic changes definitely impair the patient’s prognosis and we could not find any published research with in vivo models of regrown tumor after repeated photon or C-ion irradiations, the impact of repeated irradiations in vivo on tumor characteristics including metastatic potential and radiosensitivity need to be understood. We report the difference in alteration of these characteristics between regrown tumor after repeated photon or C-ion irradiations in vivo
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