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 |
|---|---|
| Pages (from-to) | 953-960 |
| Number of pages | 8 |
| Journal | Cell Cycle |
| Volume | 13 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2014 |
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Keywords
- 3D
- Cancer invasion
- Cell cycle kinetics
- Confocal laser microscopy
- Fluorescent proteins
- FUCCI
- Gelfoam® istoculture
- Real-time imaging
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Developmental Biology
Cite this
Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging. / Yano, Shuuya; Miwa, Shinji; Mii, Sumiyuki; Hiroshima, Yukihiko; Uehara, Fuminari; Yamamoto, Mako; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.
In: Cell Cycle, Vol. 13, No. 6, 15.03.2014, p. 953-960.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging
AU - Yano, Shuuya
AU - Miwa, Shinji
AU - Mii, Sumiyuki
AU - Hiroshima, Yukihiko
AU - Uehara, Fuminari
AU - Yamamoto, Mako
AU - Kishimoto, Hiroyuki
AU - Tazawa, Hiroshi
AU - Bouvet, Michael
AU - Fujiwara, Toshiyoshi
AU - Hoffman, Robert M.
PY - 2014/3/15
Y1 - 2014/3/15
N2 - 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.
AB - 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.
KW - 3D
KW - Cancer invasion
KW - Cell cycle kinetics
KW - Confocal laser microscopy
KW - Fluorescent proteins
KW - FUCCI
KW - Gelfoam® istoculture
KW - Real-time imaging
UR - http://www.scopus.com/inward/record.url?scp=84898015916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898015916&partnerID=8YFLogxK
U2 - 10.4161/cc.27818
DO - 10.4161/cc.27818
M3 - Article
VL - 13
SP - 953
EP - 960
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 6
ER -