Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells

Jae Won Jung, So Young Hwang, Ji Sun Hwang, Eok Soo Oh, Seokhee Park, Inn Oc Han

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1214-1224
Number of pages11
JournalEuropean Journal of Cancer
Volume43
Issue number7
DOIs
StatePublished - May 2007

Keywords

  • EMT
  • Migration
  • Radiation

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