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

Fujita, Mayumi; Imadome, Kaori; Shoji, Yoshimi; Isozaki, Tetsurou; Endo, Shunsuke; Yamada, Shigeru; Imai, Takashi

doi:10.1016/j.ijrobp.2015.05.009

Cited by 29 publications

(30 citation statements)

References 33 publications

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“…have recently demonstrated that heavy-ions could inhibit cell migration through downregulation of MMP-9 and upregulation of proadhesive cell surface integrin alpha-5 leading to increased cell adherence to extracellular matrix proteins [56]. Carbon ion is also known to reduce levels of GTP-bound Rac1 and RhoA, two important regulators of cell motility [57]. EGFR downstream signaling seems to be targeted by Carbon Ion in Lung Cancer [58], as in our study.…”

Section: Discussionsupporting

confidence: 77%

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

et al. 2016

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Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations (p < 0.05), while cetuximab only stops SQ20B migration (p < 0.005). Carbon irradiation significantly inhibits invasion in both populations (p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations (p < 0.005). These results highlight CSCs characteristics: EGFRLow, cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation.

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Section: Discussionsupporting

confidence: 77%

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

et al. 2016

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“…This increase in RBE is less about the effectiveness of carbon but more about the ineffectiveness of PhXRT with increased tumor grade (heterogeneity). In addition, unlike PhXRT which has been shown to enhance the migratory and invasiveness potential of various cancer cell lines, C-ions have consistently been shown to decrease cell migration, invasion, and matrix metalloproteinase activity across different cell lines and in in vivo tumor models [70,71,72,73,74,75,76,77]. CIRT has also been shown to modulate the immune response to tumors in mice [78,79] but very little work has been done so far on the interaction of heavy particle irradiation with the immune system.…”

Section: Preclinical Research In Carbon Ion Radiotherapymentioning

confidence: 99%

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

Mohamad

Sishc

Saha

et al. 2017

Cancers

148

130

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Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT.

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“…This impairs cellular ability for correct repair 25 and decreases the dependence of radiosensitization upon the presence of oxygen, desirable features for eradication of resilient, hypoxic tumors 5,26 . Further potential radiobiological advantages include greater RBE for killing putatively radioresistant cancer stem cells 27 and counteracting cancer invasiveness 28,29 , albeit the latter remains controversial 30 . Finally, low doses of high-LET radiation appear to elicit stronger immunological responses compared to low-LET radiation 16 .…”

Section: Introductionmentioning

confidence: 99%

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

Cirrone

Manti

Margarone

et al. 2018

Sci Rep

104

154

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Protontherapy is hadrontherapy’s fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy’s superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy’s ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

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

Abstract: In contrast to x-ray irradiation, C-ion treatment inhibited the activity of Rac1 and RhoA in MIAPaCa-2 cells and Rac1 in AsPC-1 and BxPC-3 cells via Ub-mediated proteasomal degradation, thereby blocking the motility of these pancreatic cancer cells.

Cited by 29 publications

References 33 publications

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

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