Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging

Shuya Yano, Shinji Miwa, Sumiyuki Mii, Yukihiko Hiroshima, Fuminari Uehara, Mako Yamamoto, Hiroyuki Kishimoto, Hiroshi Tazawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M. Hoffman

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39 Citations (Scopus)

Abstract

Invasive cancer cells are a critical target in order to prevent metastasis. In the present report, we demonstrate real-time visualization of cell cycle kinetics of invading cancer cells in 3-dimensional (3D) Gelfoam® histoculture, which is in vivo-like. A fluorescence ubiquitination cell cycle indicator (FUCCI) whereby G0/G1 cells express a red fluorescent protein and S/G2/M cells express a green fluorescent protein was used to determine the cell cycle position of invading and noninvading cells. With FUCCI 3D confocal imaging, we observed that cancer cells in G0/G1 phase in Gelfoam® histoculture migrated more rapidly and further than cancer cells in S/G2/M phases. Cancer cells ceased migrating when they entered S/G2/M phases and restarted migrating after cell division when the cells re-entered G0/G 1. Migrating cancer cells also were resistant to cytotoxic chemotherapy, since they were preponderantly in G0/G1, where cytotoxic chemotherapy is not effective. The results of the present report suggest that novel therapy targeting G0/G1 cancer cells should be developed to prevent metastasis.

Original languageEnglish
Pages (from-to)953-960
Number of pages8
JournalCell Cycle
Volume13
Issue number6
DOIs
Publication statusPublished - Mar 15 2014

Keywords

  • 3D
  • Cancer invasion
  • Cell cycle kinetics
  • Confocal laser microscopy
  • FUCCI
  • Fluorescent proteins
  • Gelfoam® istoculture
  • Real-time imaging

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Yano, S., Miwa, S., Mii, S., Hiroshima, Y., Uehara, F., Yamamoto, M., Kishimoto, H., Tazawa, H., Bouvet, M., Fujiwara, T., & Hoffman, R. M. (2014). Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging. Cell Cycle, 13(6), 953-960. https://doi.org/10.4161/cc.27818