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Field carcinogenesis and biological significance of the potential of the bystander effect: carcinogenesis, therapeutic response, and tissue regeneration

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Abstract

The “bystander effect” is a transmission phenomenon mediating communication from target to non-target cells, as well as cell-to-cell interactions between neighboring and distantly located cells. In this narrative review, we describe the fundamental and clinical significance of the bystander effect with respect to cell-to-cell interactions in carcinogenesis, therapeutic response, and tissue regeneration. In carcinogenesis, the bystander effect mediates communications between tumor microenvironments and non-malignant epithelial cells and has been suggested to impact heterogeneous tumorigenic cells in tumors and cancerized fields. In therapeutic response, the bystander effect mediates communications between drug-sensitive and drug-resistant cells and may transmit both drug efficacy and resistance. Therefore, control of therapeutic response transmission via the bystander effect might offer a promising future cancer treatment. Finally, in tissue regeneration, circulating cells and stromal cells may differentiate into various cells for the purpose of tissue regeneration under direction of the bystander effect arising from surrounding cells in a defective space. We hope that the findings we present will promote the development of innovative cancer therapies and tissue regeneration methodologies from the viewpoint of cell-to-cell interactions through the bystander effect.

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Acknowledgements

We thank Ms. Sayaka Okada and Ms. Kayoko Takahashi for their expert assistance.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Hiroyuki Kuwano and Takehiko Yokobori have contributed equally to this study.

Authors and Affiliations

  1. Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22, Showa-machi, Maebashi, 371-8511, Japan

    Hiroyuki Kuwano, Takehiko Yokobori, Tatsuya Miyazaki, Makoto Sohda, Tomonori Yoshida, Yoko Azuma, Hironori Tatsuki, Yasunari Ubukata, Nobuhiro Nakazawa, Kengo Kuriyama, Akihiko Sano, Makoto Sakai, Hiroomi Ogawa, Hiroshi Saeki & Ken Shirabe

  2. Fukuoka City Hospital, Fukuoka, Japan

    Hiroyuki Kuwano

  3. Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), 3-39-22 Showa-machi, Maebashi, 371-8511, Japan

    Takehiko Yokobori

  4. Division of Chest Surgery, Department of Surgery, Toho University School of Medicine, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan

    Yoko Azuma

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  1. Hiroyuki Kuwano
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Correspondence to Hiroyuki Kuwano or Takehiko Yokobori.

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Kuwano, H., Yokobori, T., Miyazaki, T. et al. Field carcinogenesis and biological significance of the potential of the bystander effect: carcinogenesis, therapeutic response, and tissue regeneration. Surg Today 53, 545–553 (2023). https://doi.org/10.1007/s00595-022-02524-5

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