title: Integrin beta1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix.
abstract: Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin beta1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin beta1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin beta1-dependent phenotype, and integrin beta1 might be a potentially effective therapeutic target in combination with radiotherapy.
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ishihara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Haga
authors.forename: Motoaki
authors.initials: M
authors.lastname: Yasuda
authors.forename: Takeomi
authors.initials: T
authors.lastname: Mizutani
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawabata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishioka
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D009361:Neoplasm Invasiveness; D011836:Radiation Tolerance; D008941:Spindle Apparatus / Q000528:radiation effects
chemical_list: D019012:Integrin beta1; D003094:Collagen