Metastasis inhibition after proton beam, β- and γ-irradiation of melanoma growing in the hamster eye.

Abstract

Standard ocular tumor treatment includes brachytherapy, as well as proton therapy, particularly for large melanoma tumors. However, the effects of different radiation types on the metastatic spread is not clear. We aimed at comparing ruthenium ((106)Ru, emitting β electrons) and iodine ((125)I, γ-radiation) brachytherapy and proton beam therapy of melanoma implanted into the hamster eye on development of spontaneous lung metastases. Tumors of Bomirski Hamster Melanoma (BHM) implanted into the anterior chamber of the hamster eye grew aggressively and completely filled the anterior chamber within 8-10 days. Metastases, mainly in the lung, were found in 100% of untreated animals 30 days after enucleation. Tumors were irradiated at a dose of 3-10 Gy with a (106)Ru plaque and at a dose of 6-14 Gy using a (125)I plaque. The protons were accelerated using the AIC-144 isochronous cyclotron operating at 60 MeV. BHM tumors located in the anterior chamber of the eye were irradiated with 10 Gy, for the depth of 3.88 mm. All radiation types caused inhibition of tumor growth by about 10 days. An increase in the number of metastases was observed for 3 Gy of β-irradiation, whereas at 10 Gy an inhibition of metastasis was found. γ-radiation reduced the metastatic mass at all applied doses, and proton beam therapy at 10 Gy also inhibited the metastastic spread. These results are discussed in the context of recent clinical and molecular data on radiation effects on metastasis.

Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of Endogenous Pigment in the Cells

“…Unlike BHM Ma cells, which become heavily pigmented after in vivo transplantation, BHM Ab cells are amelanotic. In the experiments presented here, small tumor scraps containing BHM Ma cells were transplanted in vivo by a subcutaneous injection as described previously [ 46 ]. After reaching a specific diameter [ 47 ] tumors were surgically excised and dissected into small (1–2 mm) fragments.…”

Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

“…Following the treatment with a dose of 6 Gy, the amelanotic (BHM Ab) tumors grew 2.6 times slower, and the melanotic (BHM Ma) tumors 1.4 times slower than the untreated ones. Exposure to β-radiation from 106 Ru did not significantly affect either the number or the size of metastases, except at a dose of 10 Gy, where a statistically significant decrease in the number of metastases was found in the melanotic sub-line (BHM Ma) [ 138 ]. Histological analysis showed signs of tumor blood vessel damage such as endothelial cell swelling, erythrocyte extravasation, and tumor necrosis.…”

“…A single dose of 10 Gy of proton beam irradiation delayed the growth of BHM Ma melanoma in the hamster eye by 10 days [ 138 ]. Albeit the inhibition of the implanted tumor growth was moderate, proton therapy noticeably reduced the mass of the metastases in the lung in comparison with untreated tumors ( Figure 6 ).…”

“…Representative isolated lungs with metastases from untreated ( C ) and irradiated ( D ) animals. Reproduced with permission from [ 138 ].…”

Proton Beams Inhibit Proliferation of Breast Cancer Cells by Altering DNA Methylation Status

“…The oncogenic properties of HT1080 human fibrosarcoma cells were decreased by proton irradiation in a dose-dependent manner in terms of cell migration and invasion 2 . Experimental studies to elucidate the molecular mechanisms underlying the cellular activity changes by proton beam are relatively sparse 10 , 11 . For example, vimentin, a marker of epithelial to mesenchymal transition and the metastatic properties of melanoma, was substantially decreased in proton beam-irradiated melanoma cells 12 .…”