||Bi-directional cellular signaling between microbeam targeted cancer cells and non-targeted normal cells.
Kobayashi, Alisa ,
Ahbrizal Farizal Tengku Ahmad, Tengku ,
Autsavapromporn, Narongchai ,
Shino, Homma-Takeda ,
Furusawa, YoshiyaKonishi, Teruaki
The radiation induced bystander effect (RIBE) is well known as a phenomena that causes variety of cellular responses in non-irradiated cells that surrounding the irradiated cells through propagation of damaging agents and other signals. Recently, there are reports of the RIBE are not mono-directional, but they are bi-directional between the irradiated and non-irradiated cells. Our aim is to understand the involvement of intercellular signaling between targeted human lung carcinoma cells and non-targeted normal cells which is relevant to radio-therapy. For this purpose, we used SPICE-NIRS microbeam that provides 3.4 MeV proton beam in micrometer size that can precisely target only the cancer cells in the mixed population with normal cells. We found that surrounding normal cells enhances the repair of DNA double strand break of targeted cancer cells through gap-junction intercellular communication (GJIC), while surrounding non-irradiated cells were damaged through both GJIC and media secret factors, such as nitric oxide (NO). In addition, the DSB induction in bystander-cancer cells was affected by the surrounding non-irradiated normal cells. As a conclusion, our findings indicate that the radio-sensitivity of cancer cells is modified through bi-directional cellular communication with surrounding normal cells.
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