In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.
Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast.
Ikeda
Kenji
K
Osaka Ohtani University, Japan. ikedak@osaka-ohtani.ac.jp
Utoguchi
Naoki
N
Tsutsui
Hidenobu
H
Yamaue
Satoko
S
Homemoto
Manami
M
Nakao
Erina
E
Hukunaga
Yumi
Y
Yamasaki
Kyohei
K
Myotoku
Michiaki
M
Hirotani
Yoshihiko
Y
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D005617:Chlorofluorocarbons, Methane / Q000493:pharmacokinetics; D002822:Choriocarcinoma / Q000378:metabolism*; D003470:Culture Media; D017097:Electric Impedance; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D046509:Tissue Culture Techniques; D057900:Transcytosis; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015820:Cadherins; D005617:Chlorofluorocarbons, Methane; D003470:Culture Media; C476884:HOPX protein, human; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C086960:osteoblast cadherin; C007782:dichlorodifluoromethane