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
N1 - Funding Information:
Acknowledgments This work was supported by Mid-career Researcher Program through NRF Grant funded by the MEST (No. 2012R1A2A2A01003361) and the Nano-Biotechnology Project (Regenomics, 2011-0007745) of the Korean Science and Engineering Foundation (KOSEF). Yu-Jin Kim was sponsored by the Ministry of Knowledge Economy (MKE) and Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/5
Y1 - 2013/5
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 -