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Breast Cancer Research and Treatment

, Volume 167, Issue 2, pp 439–450 | Cite as

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

  • Yayoi Adachi
  • Mayumi Yoshimura
  • Keiko Nishida
  • Hisanobu Usuki
  • Keiko Shibata
  • Masaya Hattori
  • Naoto Kondo
  • Yasushi Yatabe
  • Hiroji Iwata
  • Toyone Kikumori
  • Yasuhiro Kodera
  • Hayao Nakanishi
Preclinical study

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.

Keywords

CTC In vivo dynamics Cytology Breast cancer Chemotherapy Preclinical study 

Notes

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.

Compliance with ethical standards

Conflict of interest

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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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yayoi Adachi
    • 1
    • 2
  • Mayumi Yoshimura
    • 3
  • Keiko Nishida
    • 3
  • Hisanobu Usuki
    • 4
  • Keiko Shibata
    • 4
  • Masaya Hattori
    • 2
  • Naoto Kondo
    • 2
  • Yasushi Yatabe
    • 3
  • Hiroji Iwata
    • 2
  • Toyone Kikumori
    • 1
  • Yasuhiro Kodera
    • 5
  • Hayao Nakanishi
    • 3
    • 4
  1. 1.Department of Transplantation and Endocrine SurgeryNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Breast OncologyAichi Cancer Center Central HospitalNagoyaJapan
  3. 3.Department of Pathology and Molecular DiagnosticsAichi Cancer Center Central HospitalNagoyaJapan
  4. 4.Laboratory of Pathology and Clinical ResearchAichi Cancer Center Aichi HospitalOkazakiJapan
  5. 5.Department of Gastroenterological SurgeryNagoya University Graduate School of MedicineNagoyaJapan

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