X‐ray irradiation and Rho‐kinase inhibitor additively induce invasiveness of the cells of the pancreatic cancer line, MIAPaCa‐2, which exhibits mesenchymal and amoeboid motility

Abstract

Tumor cells can migrate and invade tissue by two modes of motility: mesenchymal and amoeboid. X-ray or c-ray irradiation increases the invasiveness of tumor cells with mesenchymal motility through the induction of matrix metalloproteinases (MMP), and this increase is suppressed by MMP inhibitors (MMPI). However, the effects of X-ray or c-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 exhibits both modes of motility. The X-ray-induced invasiveness of MIAPaCa-2 cells was associated with the upregulation of MMP2 at both the RNA and protein levels and was inhibited by MMPI treatment. Amoeboid-mesenchymal transition was slightly induced after irradiation. The MMPI treatment caused mesenchymal-amoeboid transition without significant increase in invasiveness, while the 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 nonirradiated conditions. (Cancer Sci 2011; 102: 792-798) P ancreatic cancer is one of the most aggressive diseases with an extremely low 5-year survival rate. (1,2) Most patients with pancreatic cancer have advanced disease at the time of diagnosis, and this disease is associated with a high metastatic potential, which is a major clinical problem. (1,3) Chemotherapy and radiotherapy are used as adjuvants to surgery and for palliative purposes in cases where surgical resection is not feasible. However, it has been reported that there is no clear evidence to indicate that intraoperative radiotherapy is more effective than other therapies in treating pancreatic cancer in locally advanced and metastatic stages. (4) Further characterization of pancreatic cancer cells exposed to anti-tumor drugs and irradiation is required to develop methods for improving treatment strategies.It remains to be determined whether the application of local radiotherapy affects the characteristics of subsequently appearing metastatic tumors. Several studies have shown that conventional X-ray or c-ray irradiation itself induces the metastasis of pancreatic tumor cells both in vitro and in vivo. (1,3,(5)(6)(7) These studies revealed that photon-irradiated cells produce proteases, such as matrix metalloproteinase...

Irradiation affects cellular properties and Eph receptor expression in human melanoma cells

“…The data from the literature concerning irradiation effects on migration and invasion are controversial depending on tumor entity. Some authors detected an irradiation-induced increase in migration and invasion in glioma and pancreatic cell lines, 12,13 while other authors found an irradiation-induced decrease in lung adenocarcinoma, colorectal carcinoma or sarcoma cell lines. 4,9,16 However, the detected differences between individual melanoma cell lines in irradiation-induced changes in metastasis-relevant properties as well as in Eph/ephrin expression seem to base rather on genetic or epigenetic background than on origin of the cell lines.…”

“…In this regard, an irradiation-induced increase in substrate adhesion was demonstrated for mouse melanoma, fibrosarcoma cells and lung cancer. 2,[8][9][10][11] Furthermore, irradiation was found to increase motility, migration and invasion in glioma, pancreatic cancer, non-small-cell lung cancer 8,[11][12][13] and also to increase metastasis in vivo. 10,14,15 Further, increasing migration at low doses has been described, followed by a decrease at higher doses.…”

Carbon-Ion Irradiation Suppresses Migration and Invasiveness of Human Pancreatic Carcinoma Cells MIAPaCa-2 via Rac1 and RhoA Degradation

“…A C C E P T E D ACCEPTED MANUSCRIPT 3 In cancer, carbon (C)-ion irradiation has advantages over conventional photon therapy, such as accurate dose distribution and enhanced biological effects due to higher linear energy transfer (LET) translated into two-to three-fold higher cytotoxicity as evidenced by the analysis of biological endpoints, including cell death, DNA damage, and chromosomal aberrations (1,2).…”

Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells

“…Radiotherapy has been found to promote the invasion of various kinds of cancer cells including GBM [5][6][7][8][9]. Ionizing radiation (IR) activates multiple signalling pathways in tumour cells, which modulate several cellular functions and induce the secretion of growth factors and chemokines, resulting in increased migration and invasiveness of cancer cells [10][11][12].…”