Abstract
Purpose
The identification of novel cell lines which combine the most important properties of mucosal membranes in terms of drug absorption, transmembrane transport and mucus secretion can help to establish improved and meaningful test systems for pharmacological and infectiological studies.
Methods
We have established a novel mucus secreting tumor cell line (Cx-03) derived from a female patient who underwent radical hysterectomy after diagnosis of a large malignant carcino sarcoma (Muellerian mixed tumor). Via xenotransplantation in SCID beige mice, recultivation and subcloning a stable cell line was established from primary tumor cells.
Results
Human origin and novelty of the cell line was determined by karyotype analysis and STR fingerprint. During growth cells produce considerable amounts of a PAS positive viscoelastic mucus. Immunostaining revealed expression of mucins and the mucin modifier CLCA1. We demonstrate in initial electrophysiological experiments that confluent, polarized monolayers of Cx-03 are formed (on PCF-filter supports) that exhibit stable electrical resistance (> 600 Ω cm2). Confluent Cx-03 monolayers express barrier-forming tight junction proteins claudin-1 and -4 which co-localize with zonula occludens protein-1 (ZO-1) at cell-cell contacts.
Conclusions
Mucus secretion is a rare property among mammalian cell lines. In combination with its ability to form polarized monolayers Cx-03 might contribute as a novel cell based model for drug absorption, transport and barrier studies.
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ACKNOWLEDGMENTS AND DISCLOSURES
The study was supported by the Berliner Krebsgesellschaft and the Wilhelm-Sander-Stiftung. The authors would like to thank Prof. Heidemarie Neitzel and Prof. Martin Digweed from the Institute of Genetics (Charité University Medicine Berlin, Germany) for their excellent support. The technical assistance of In-Fah Maria Lee is gratefully acknowledged.
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Bücker, R., Schaefer, C., Gruber, A.D. et al. Establishment of a Mucin Secreting Cell Line Cx-03 from an Uterine Carcino Sarcoma. Pharm Res 36, 7 (2019). https://doi.org/10.1007/s11095-018-2533-z
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DOI: https://doi.org/10.1007/s11095-018-2533-z