Increased motility and invasiveness in tumor cells that survive 10 Gy irradiation.
Radiotherapy is an important noninvasive treatment for many types of cancer. However, it has been reported that the proliferative, invasive, and metastatic capacities of tumor cells can be increased in the repopulated tumors that survive radiotherapy. We have previously established a radiation-surviving cell model for the human non-small cell lung cancer cell line H1299 by harvesting relic cells 14 days after irradiation (IR cells). Here, we report that cell invasion, cell migration, and cell adhesion are enhanced in these surviving cancer cells. The mRNA expression levels of matrix metalloproteinases (MMPs), including mmp1, mmp2, and mmp9, were upregulated in IR cells compared with parental cells. A gelatin zymogram, wound healing assay, and invasion assay showed increased MMP activity, cell motility, and invasiveness in IR cells, respectively. Moreover, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, paxillin, phosphorylated FAK, integrin beta1, and vinculin were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. In this report, we identify molecules responsible for the malignant properties of tumor cells that survive irradiation. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.
Tsutsumi
Kaori
K
Department of Biomedical Science and Engineering, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan. tsutsumi@hs.hokudai.ac.jp
Tsuda
Masumi
M
Yazawa
Natsuka
N
Nakamura
Hirotaka
H
Ishihara
Seiichiro
S
Haga
Hisashi
H
Yasuda
Motoaki
M
Yamazaki
Rie
R
Shirato
Hiroki
H
Kawaguchi
Hideaki
H
Nishioka
Takeshi
T
Ohba
Yusuke
Y
D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000532:radiotherapy*; D002448:Cell Adhesion / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects*; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism / Q000528:radiation effects; D008175:Lung Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism / Q000528:radiation effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism / Q000528:radiation effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism / Q000528:radiation effects; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000378:metabolism / Q000528:radiation effects; D011829:Radiation Dosage; D016596:Vinculin / Q000378:metabolism / Q000528:radiation effects
D019012:Integrin beta1; D051419:Paxillin; D016596:Vinculin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1