Abstract
Multicellular layers (MCL) of cancer cells is an in vitro 3-dimensional (3D) model that mimics avascular microregions of human solid tumors and has been shown to be useful in pharmacokinetic-pharmacodynamic studies of anticancer agents. We investigated whether Ki-67, which is widely used as a proliferation marker, can be used to evaluate changes in proliferative fractions following drug exposure in MCL of HT-29 human colorectal cancer cells. Ki-67 expression was monitored and compared between cancer cells cultured as monolayers or MCL. Drug distribution and Ki-67 expression were evaluated within MCL following exposure to doxorubicin and paclitaxel. Ki-67 expression was observed in the nuclei of proliferating cells in monolayers, tumor xenograft, and multicellular spheroids. In MCL, however, Ki-67 expression was detected in the membrane/cytoplasm as well as in the nucleus throughout MCL. Neither the location nor the level of expression changed following drug exposure, whereas drug-induced apoptosis increased. Our data show that membranous/cytoplasmic Ki-67 may not be valid as a marker for the proliferative activity of cells grown as MCL. Studies for non-nuclear localization and its mechanism in 3D in vitro models of other cell lines are warranted.
| Original language | English |
|---|---|
| Pages (from-to) | 634-640 |
| Number of pages | 7 |
| Journal | Archives of Pharmacal Research |
| Volume | 36 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2013 May 1 |
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Keywords
- HT-29 human colorectal cancer cells
- Ki-67
- Multicellular layer
- Multicellular spheroid
- Proliferation marker
- Three-dimensional culture
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
- Organic Chemistry
Cite this
Non-nuclear localization of Ki-67 in human colorectal cancer cells grown as multicellular layers. / Kim, Yu Jin; Lee, Sang Hoon; Lee, Jaehwi; Kuh, Hyo Jeong.
In: Archives of Pharmacal Research, Vol. 36, No. 5, 01.05.2013, p. 634-640.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Non-nuclear localization of Ki-67 in human colorectal cancer cells grown as multicellular layers
AU - Kim, Yu Jin
AU - Lee, Sang Hoon
AU - Lee, Jaehwi
AU - Kuh, Hyo Jeong
PY - 2013/5/1
Y1 - 2013/5/1
N2 - Multicellular layers (MCL) of cancer cells is an in vitro 3-dimensional (3D) model that mimics avascular microregions of human solid tumors and has been shown to be useful in pharmacokinetic-pharmacodynamic studies of anticancer agents. We investigated whether Ki-67, which is widely used as a proliferation marker, can be used to evaluate changes in proliferative fractions following drug exposure in MCL of HT-29 human colorectal cancer cells. Ki-67 expression was monitored and compared between cancer cells cultured as monolayers or MCL. Drug distribution and Ki-67 expression were evaluated within MCL following exposure to doxorubicin and paclitaxel. Ki-67 expression was observed in the nuclei of proliferating cells in monolayers, tumor xenograft, and multicellular spheroids. In MCL, however, Ki-67 expression was detected in the membrane/cytoplasm as well as in the nucleus throughout MCL. Neither the location nor the level of expression changed following drug exposure, whereas drug-induced apoptosis increased. Our data show that membranous/cytoplasmic Ki-67 may not be valid as a marker for the proliferative activity of cells grown as MCL. Studies for non-nuclear localization and its mechanism in 3D in vitro models of other cell lines are warranted.
AB - Multicellular layers (MCL) of cancer cells is an in vitro 3-dimensional (3D) model that mimics avascular microregions of human solid tumors and has been shown to be useful in pharmacokinetic-pharmacodynamic studies of anticancer agents. We investigated whether Ki-67, which is widely used as a proliferation marker, can be used to evaluate changes in proliferative fractions following drug exposure in MCL of HT-29 human colorectal cancer cells. Ki-67 expression was monitored and compared between cancer cells cultured as monolayers or MCL. Drug distribution and Ki-67 expression were evaluated within MCL following exposure to doxorubicin and paclitaxel. Ki-67 expression was observed in the nuclei of proliferating cells in monolayers, tumor xenograft, and multicellular spheroids. In MCL, however, Ki-67 expression was detected in the membrane/cytoplasm as well as in the nucleus throughout MCL. Neither the location nor the level of expression changed following drug exposure, whereas drug-induced apoptosis increased. Our data show that membranous/cytoplasmic Ki-67 may not be valid as a marker for the proliferative activity of cells grown as MCL. Studies for non-nuclear localization and its mechanism in 3D in vitro models of other cell lines are warranted.
KW - HT-29 human colorectal cancer cells
KW - Ki-67
KW - Multicellular layer
KW - Multicellular spheroid
KW - Proliferation marker
KW - Three-dimensional culture
UR - http://www.scopus.com/inward/record.url?scp=84878232590&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878232590&partnerID=8YFLogxK
U2 - 10.1007/s12272-013-0061-2
DO - 10.1007/s12272-013-0061-2
M3 - Article
C2 - 23536320
AN - SCOPUS:84878232590
VL - 36
SP - 634
EP - 640
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
SN - 0253-6269
IS - 5
ER -