Received for publication June 9, 2006.
Revised September 21, 2006.
Accepted for publication September 29, 2006.

Organic anion transporting polypeptide 2B1 and breast cancer resistance protein interact in the transepithelial transport of steroid sulfates in human placenta

Abstract

The human placenta has both protective and nurturing functions for the fetal organism. Uptake and elimination of xenobiotics and endogenous substances are facilitated by various transport proteins from the SLC- and ABC-families, respectively. A functional interaction of uptake and elimination, which is a prerequisite for vectorial transport across cellular barriers, has not been described for placenta. In this study we examined expression of OAT4 (SLC22A11), OATP2B1 (SLCO2B1, OATP-B) and BCRP (ABCG2) in human placenta (n=71), since all three proteins are involved in transmembranal transfer of estrone-3-sulfate (E3S; metabolic product) and dehydroepiandrosterone-sulfate (DHEAS; precursor molecule). On mRNA level we found a significant correlation between OATP2B1 and BCRP (R² = 0.534; P < 0.01) but not between OAT4 and BCRP (R² = -0.104; P > 0.05). Localization studies confirmed basal expression of OATP2B1 and apical expression of BCRP. To study functional interactions between OATP2B1 and BCRP we developed an MDCKII cell model expressing both transport proteins simultaneously (OATP2B1 and BCRP in the basal and apical membrane, respectively). Employing this cell model in a transwell system resulted in a significantly increased basal to apical transport of both E-3-S and DHEAS, when both transporters were expressed with no change of transfer in the apical to basal direction. Taken together these data demonstrate the potential for a functional interaction of OATP2B1 and BCRP in transepithelial transport of steroid sulfates in human placenta.

Key words: ABC transporters, organic anion transport, steroids, transporters

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