In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells

Basic Clin Pharmacol Toxicol. 2011 Feb;108(2):138-45. doi: 10.1111/j.1742-7843.2010.00634.x. Epub 2010 Oct 18.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism
  • Cadherins / metabolism
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Membrane Permeability
  • Chlorofluorocarbons, Methane / pharmacokinetics
  • Choriocarcinoma / metabolism*
  • Culture Media
  • Electric Impedance
  • Homeodomain Proteins / metabolism
  • Humans
  • Models, Biological
  • Neoplasm Proteins / metabolism
  • Tissue Culture Techniques
  • Transcytosis*
  • Trophoblasts / cytology*
  • Trophoblasts / metabolism*
  • Tumor Suppressor Proteins / metabolism

Substances

  • ABCB1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Cadherins
  • Chlorofluorocarbons, Methane
  • Culture Media
  • HOP protein, human
  • Homeodomain Proteins
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • osteoblast cadherin
  • dichlorodifluoromethane