@article{oai:repo.qst.go.jp:00047660, author = {Fujita, Mayumi and Otsuka, Yoshimi and Yamada, Shigeru and Iwakawa, Mayumi and Imai, Takashi and 藤田 真由美 and 荘司 好美 and 山田 滋 and 岩川 眞由美 and 今井 高志}, issue = {4}, journal = {Cancer Science}, month = {Feb}, note = {Tumor cells can migrate and invade tissue by 2 modes of motility—mesenchymal and amoeboid. X-ray or gamma-ray irradiation increases the invasiveness of tumor cells with mesenchymal motility through the induction of matrix metalloproteinases (MMPs), and this increase is suppressed by MMP inhibitors (MMPIs). However, the effects of X-ray or gamma-ray irradiation on the invasiveness of tumor cells with amoeboid motility remain unclear. We investigated the effect of irradiation on amoeboid motility by using cells of the human pancreatic cancer line, MIAPaCa-2, which exhibit both modes of motility. The X-ray-induced invasiveness of MIAPaCa-2 cells was associated with the upregulation of MMP2 at both RNA and protein levels and was inhibited by MMPI treatment. Amoeboid–mesenchymal transition was slightly induced after irradiation. MMPI treatment caused mesenchymal–amoeboid transition without significant increase in invasiveness while ROCK inhibitor (ROCKI) stimulated amoeboid–mesenchymal transition and enhanced invasiveness under both non-irradiated and irradiated conditions. This ROCKI-induced transition was accompanied by the upregulation of MMP2 mRNA and protein. Exposure to both irradiation and ROCKI further enhanced MMP2 expression and had an additive effect on the invasiveness of MIAPaCa-2 cells. Additionally, exposure to MMPI led to significant suppression of both radiation-induced and the basal invasiveness of MIAPaCa-2 cells. This suggests that ROCKI treatment, especially with concomitant X-ray irradiation, can induce invasion of cancer cells and should be used only for certain types of cancer cells. Simultaneous use of inhibitors, ROCKI and MMPI may be effective in suppressing invasiveness under both X-ray-irradiated and non-irradiated conditions.}, pages = {792--798}, title = {X-ray irradiation and Rho-kinase inhibitor additively induce invasiveness of the cells of the pancreatic cancer line, MIAPaCa-2, which exhibit mesenchymal and amoeboid motility}, volume = {102}, year = {2011} }