Tumor and Stem Cell Biology Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays

Although carbon ion therapy facilities are expensive, the biological effects of carbon ion beam treatment may be better against cancer (and cancer stem cells) than the effects of a photon beam. To investigate whether a carbon ion beam may have a biological advantage over X-rays by targeting cancer stem–like cells, human colon cancer cells were used in vitro and in vivo. The in vitro relative biological effectiveness (RBE) values of a carbon ion beam relative to X-rays at the D10 values were from 1.63 to 1.74. Cancer stem–like CD133þ, CD44þ/ESAþ cells had a greater ability for colony and spheroid formation, as well as in vivo tumorigenicity compared with the CD133 , CD44 /ESA cells. FACS (fluorescence-activated cell sorting) data showed that cancer stem–like cells were more highly enriched after irradiation with X-rays than carbon ion at doses that produced the same level of biological efficacy. A colony assay for cancer stem–like cells showed that RBE values calculated by the D10 levels were from 2.05 to 2.28 for the carbon ion beam relative to X-rays. The in vivo xenotransplant assay showed an RBE of 3.05 to 3.25, calculated from the slope of the dose–response curve for tumor growth suppression. Carbon ion irradiation with 15 Gy induced more severe xenograft tumor cell cavitation and fibrosis without significant enhancement of cells with putative cancer stem cell markers, CD133, ESA, and CD44, compared with 30 Gy X-rays, and marker positive cells were significantly decreased following 30 Gy carbon ion irradiation. Taken together, carbon ion beam therapy may have an advantage over photon beam therapy by improved targeting of putative colon cancer stem–like cells. Cancer Res; 71(10); 3676–87. 2011 AACR.