Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells.
Radiotherapy remains a major therapeutic option for patients with advanced lung cancer. Nevertheless, the effects of irradiation on malignant biological behaviours (e.g. migration and transformation of cancer cells) have yet to be clarified. We conducted an in vitro study to investigate the radiation-induced alterations including morphology, adhesion, and cell motility of A549 human lung cancer cells. These changes, which are associated with epithelial-mesenchymal transdifferentiation (EMT), seem to be linked to radiation-induced fibrosis, which represents one of the most common long-term adverse effects of curative radiotherapy. In addition, loss of intercellular adhesion and increased cell motility may be involved in post-radiotherapy-associated metastasis. We showed that stress fibres and focal adhesions are increased and that cell-cell junctions are decreased in response to ionising radiation. Radiation also significantly increased cell motility. The p38-specific inhibitor, SB203580, reduced the radiation-promoted migration of A549 cells, whereas SP600125, a JNK MAPK-specific inhibitor, inhibited both inherent and radiation-mediated cell motility. Consistent with this observation, radiation up-regulated the phosphorylation of p38 MAPK. Current approaches to cancer treatment involving more intensive radiotherapy regimens have been suggested to be associated with a higher incidence of local or distant metastasis. Therefore, a subset of patients may benefit from a combination of radiotherapy with inhibitors of EMT or cell migration.
Jung
Jae-Won
JW
Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Korea.
Hwang
So-Young
SY
Hwang
Ji-Sun
JS
Oh
Eok-Soo
ES
Park
Seokhee
S
Han
Inn-Oc
IO
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000473:pathology*; D002448:Cell Adhesion / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D004847:Epithelial Cells / Q000473:pathology / Q000528:radiation effects*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000199:Actins; D051419:Paxillin; D012333:RNA, Messenger; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases