title: Effects of carbon ion beam on putative colon cancer stem cells and its comparison with X-rays.
abstract: 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 CD133(+), CD44(+)/ESA(+) 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.
authors: Heavy-Ion Radiobiology Research Group, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences (NIRS), Chiba, Japan. saisei@nirs.go.jp
authors: Xing
authors: X
authors: Cui
authors: Kazuhiko
authors: K
authors: Oonishi
authors: Hirohiko
authors: H
authors: Tsujii
authors: Takeshi
authors: T
authors: Yasuda
authors: Yoshitaka
authors: Y
authors: Matsumoto
authors: Yoshiya
authors: Y
authors: Furusawa
authors: Makoto
authors: M
authors: Akashi
authors: Tadashi
authors: T
authors: Kamada
authors: Ryuichi
authors: R
authors: Okayasu
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002244:Carbon / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002469:Cell Separation; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis; D063193:Heavy Ion Radiotherapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000528:radiation effects*; D010455:Peptides; D011878:Radiotherapy / Q000379:methods; D014965:X-Rays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D002244:Carbon