Carbon‐ion radiation enhances migration ability and invasiveness of the pancreatic cancer cell, PANC‐1, in vitro

Abstract

Pancreatic cancer is an aggressive disease that responds poorly to conventional photon radiotherapy. Carbon‐ion (C‐ion) radiation has advantages compared with conventional radiotherapy, because it enables more accurate dose distribution and more efficient tumor cell killing. To elucidate the effects of local radiotherapy on the characteristics of metastatic tumors, it is necessary to understand the nature of motility in irradiated tumor cells; this will, in turn, facilitate the development of effective strategies to counter tumor cell motility, which can be used in combination with radiotherapy. The aim of the present study was to examine the invasiveness of pancreatic cancer cells exposed to C‐ion irradiation. We found that C‐ion irradiation suppressed the migration of MIAPaCa‐2, BxPC‐3 and AsPC‐1; diminished the invasiveness of MIAPaCa‐2; and tended to reduce the invasion of BxPC‐3 and AsPC‐1. However, C‐ion irradiation increased the invasiveness of PANC‐1 through the activation of plasmin and urokinase‐type plasiminogen activator. Administration of serine protease inhibitor (SerPI) alone failed to reduce C‐ion‐induced PANC‐1 invasiveness, whereas the combination of SerPI and Rho‐associated coiled‐coil forming protein kinase (ROCK) inhibitor suppressed it. Furthermore, PANC‐1 showed mesenchymal–amoeboid transition when we treated with SerPI alone. In conclusion, C‐ion irradiation is effective in suppressing the invasive potential of several pancreatic tumor cell lines, but not PANC‐1; this is the first study showing that C‐ion irradiation induces the invasive potential of a tumor cell line. Further in vivo studies are required to examine the therapeutic effectiveness of radiotherapy combined with inhibitors of both mesenchymal and amoeboid modes of tumor cell motility. (Cancer Sci 2012; 103: 677–683)

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

“…their migration and invasion (4). Here, we found that C-ion irradiation at 0.5, 1, 2, and 4 Gy dose-dependently inhibited the migration and invasion of MIAPaCa-2 cells (Fig.…”

“…Furthermore, we found that in AsPC-1 and BxPC-3 cells, C-ion irradiation also significantly decreased the levels of GTP-bound Rac1 without affecting total Rac1 expression (Fig. 4C, D), which correlated with the inhibition of cell migration (4). The decrease in GTP-bound Rac1 was rescued by the treatment with epoxomicin (Fig.…”

“…It has been previously reported that C-ion and photon radiation produced different effects on the migration and invasiveness of tumor cells (3)(4)(5). X-ray irradiation enhanced the invasiveness of MIAPaCa-2 and PANC-1 pancreatic cancer cells (3,4), whereas C-ions suppressed invasion and migration of MIAPaCa-2 as well as BxPC-3 and AsPC-1 pancreatic adenocarcinoma cells (4), but enhanced PANC-1 cell invasion (4).…”

“…Cell movement requires dynamic remodeling of cellular architecture, including actin filament rearrangement and actomyosin contraction, and Rho GTPases Rac1 and RhoA are key components of signaling networks regulating cell migration (6). We have previously demonstrated that nitric oxide-induced RhoA activation enhanced the invasiveness of C-ion-irradiated PANC-1 cells (4). However, the role of Rac1 and RhoA in the response of cancer cells to C-ion irradiation has not been explored.…”

“…X-ray irradiation enhanced the invasiveness of MIAPaCa-2 and PANC-1 pancreatic cancer cells (3,4), whereas C-ions suppressed invasion and migration of MIAPaCa-2 as well as BxPC-3 and AsPC-1 pancreatic adenocarcinoma cells (4), but enhanced PANC-1 cell invasion (4). Cell movement requires dynamic remodeling of cellular architecture, including actin filament rearrangement and actomyosin contraction, and Rho GTPases Rac1 and RhoA are key components of signaling networks regulating cell migration (6).…”