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 language | English |
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Pages (from-to) | 953-960 |
Number of pages | 8 |
Journal | Cell Cycle |
Volume | 13 |
Issue number | 6 |
DOIs | |
Publication status | Published - 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