title: Radiation induces epithelial-mesenchymal transition in colorectal cancer             cells.
abstract: Radiotherapy remains a major approach to adjuvant therapy for patients with             advanced rectal cancer. Nevertheless, the effects of radiation on malignant processes             have yet to be clarified. The aim of this study was to assess the biological effects             of radiation on colorectal cancer (CRC) cells with special reference to epithelial-mesenchymal             transition (EMT), a key developmental program often activated during cancer invasion             and metastasis. We investigated the effect of radiation on two colorectal cancer             cell lines, CaR1 and DLD1, assessing cell morphology, motility, migration and             invasive ability. Expression of molecules associated with EMT was determined using             RT-PCR, Western blotting, and immunofluorescence staining in control and irradiated             cells. We also used real-time RT-PCR to examine the expression of molecules associated             with EMT before and after chemoradiotherapy. Thus, we studied 26 rectal cancer             patients who received preoperative chemoradiotherapy followed by radical surgery.             In addition, we examined the relationship between disease recurrence and the expression             of a number of proteins. Irradiation caused CRC cells to undergo phenotypic changes             characteristic of EMT: spindle-cell shape, loss of polarity, intercellular separation             and pseudopodia formation. Irradiation enhanced cell migration and invasiveness.             In irradiated CRC cells, molecular changes consistent with EMT were observed.             In clinical samples, we observed molecular changes consistent with EMT, and those             changes were significantly enhanced in patients with recurring disease. These             results indicate that irradiation induces an alteration to a malignant phenotype             consistent with EMT in colorectal cancer cells.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. ayayaka@clin.medic.mie-u.ac.jp
authors.forename: Aya
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoe
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Chikao
authors.initials: C
authors.lastname: Miki
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000528:radiation effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011878:Radiotherapy / Q000009:adverse effects*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction