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Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin chemotherapy in breast cancer mouse models

  • Preclinical study
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Abstract

Purpose

Circulating tumor cells (CTCs) can provide a potentially minimal invasive source for monitoring chemotherapeutic effects. However, detailed in vivo dynamics of CTC after chemotherapy remain largely unknown.

Methods

We monitored CTC number and morphology early after chemotherapy using a newly developed cytology-based CTC detection device and triple-negative breast cancer mouse CTC models with spontaneous lung metastatic potential.

Results

Paclitaxel inhibited cell growth of breast cancer cells by mainly G2/M cell cycle arrest and partly apoptosis, whereas doxorubicin inhibited cell growth mainly by apoptosis and partly G2 cell cycle arrest in vitro. The number of CTCs was significantly increased 3–10 days after paclitaxel and doxorubicin chemotherapy and decreased thereafter in two mouse CTC models. The transiently increased CTCs early post-chemotherapy consisted of not only G2/M arrested cells (apoptotic cells), but also morphologically near-intact live cells. This heterogeneous cell population of CTCs was similar to that of primary tumor tissue after chemotherapy.

Conclusions

These results indicate that CTCs can be mobilized from the primary tumor in rapid response to chemotherapy and suggest the possibility that CTC monitoring from both numerical and morphological viewpoints early after chemotherapy using a cytology-based CTC detection device would be a useful diagnostic tool for predicting drug sensitivity/resistance in preclinical and clinical setting.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for Priority Research Project from Knowledge Hub Aichi, Japan and Ministry of Education, Science, Sports, Culture and Technology, Japan.

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Authors and Affiliations

  1. Department of Transplantation and Endocrine Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8560, Japan

    Yayoi Adachi & Toyone Kikumori

  2. Department of Breast Oncology, Aichi Cancer Center Central Hospital, 1-1 Kanokoden, Chikusa, Nagoya, 464-8681, Japan

    Yayoi Adachi, Masaya Hattori, Naoto Kondo & Hiroji Iwata

  3. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, 1-1, Kanokoden, Chikusa, Nagoya, 464-8681, Japan

    Mayumi Yoshimura, Keiko Nishida, Yasushi Yatabe & Hayao Nakanishi

  4. Laboratory of Pathology and Clinical Research, Aichi Cancer Center Aichi Hospital, 18 Kuriyada Kakemachi, Okazaki, 444-0011, Japan

    Hisanobu Usuki, Keiko Shibata & Hayao Nakanishi

  5. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8560, Japan

    Yasuhiro Kodera

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  1. Yayoi Adachi
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  2. Mayumi Yoshimura
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  12. Hayao Nakanishi
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Corresponding author

Correspondence to Hayao Nakanishi.

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The authors have no conflict of interest.

Ethical approval

All animal experiments were performed under the experiment protocol approved by the Ethics Review Committee of the Aichi Cancer Center.

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Adachi, Y., Yoshimura, M., Nishida, K. et al. Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin chemotherapy in breast cancer mouse models. Breast Cancer Res Treat 167, 439–450 (2018). https://doi.org/10.1007/s10549-017-4532-x

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  • DOI: https://doi.org/10.1007/s10549-017-4532-x

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