Modulation of transferrin-receptor activity and recycling after induced differentiation of BeWo choriocarcinoma cells

Abstract

BeWo human choriocarcinoma cells normally grow as cytotrophoblast cells. However, in the presence of 100 ,M-forskolin or 5 mM-theophylline, these cells form syncytia similar to morphologically well differentiated syncytiotrophoblasts. We have examined the effect of syncytia formation on transferrin-receptor activity and recycling. Although cellular proliferation stops upon growth in the presence of forskolin or theophylline, the number of cell-surface transferrinreceptors unexpectedly increased 2-fold, whereas the total cellular number increased at most 15 %. The rate of biosynthesis of the transferrin receptor as well as class I MHC glycoprotein did not change measurably during syncytium formation. The biosynthesis of human chorionic gonadotropin increased 35-fold after 30 h of growth in the presence of theophylline. The redistribution of the transferrin receptor in syncytia is maintained by a decreased rate constant of endocytosis (0.141 min-' compared with 0.231 min-' for control cells) and an increased rate constant of externalization (0.122 min-1 compared with 0.060 min-' for control cells). These altered rates of endocytosis and externalization resulted in an increased rate of iron accumulation in the syncytia. Furthermore, the recycling time of the transferrin receptor decreased in cells grown in the presence of theophylline (14.6 min compared with 21.2 min in control cells).

Carrier-mediated transport of monocarboxylic acids in BeWo cell monolayers as a model of the human trophoblast

“…16 BeWo cell monolayers have been applied to studies of the polarized trans-trophoblast transport of serotonin and transferrin, monoamine uptake processes, and relevant nutrient uptake and transport systems. [16][17][18] The existence of MCT systems in the BeWo cells would provide an in vitro tool representative of the human trophoblast to characterize trans-placental transport mechanisms that influence drug distribution in pregnancy. The BeWo cell line is particularly attractive for the studies of drug distribution at the placenta barrier because it is stable, relatively easy to maintain by passage, and grows to a confluent monolayer in relatively short period of time.…”

Placental ceruloplasmin homolog is regulated by iron and copper and is implicated in iron metabolism

“…When grown on porous filters, BeWo cells have the ability to form a polarized monolayer and display directional transport features, both of which cannot be observed in cells grown on a plastic surface (7,8,10,27). Furthermore, BeWo cells have been used extensively as a model to study placental Fe uptake and flux (7,8,(34)(35)(36). Using the BeWo cell line, we have presented evidence for an endogenous membrane-bound homolog to Cp, similar to hephaestin in the gut (10).…”

Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier

“…The BeWo cell line is a choriocarcinoma cell line developed from a malignant gestational choriocarcinoma of the fetal placenta and was characterized in 1968 (17). This cell line has been shown to exhibit morphological and biochemical characteristics, similar to the human trophoblasts and the presence of nutrient and serotonin transporters (18)(19)(20) . In addition, the BeWo cell line is stable, easy to maintain by passage and forms confluent monolayers on polycarbonate filters in a relatively short period of time (4-5 days), making it an attractive in vitro model to study trans-trophoblast transport, uptake and metabolism of drugs.…”