ABC transporters do not contribute to extracellular translocation of hyaluronan in human breast cancer in vitro

Experimental Cell Research
Natalie K Thomas, Tracey J Brown

Abstract

Extracellular translocation of the polysaccharide, hyaluronan (HA) has been thought to be mediated via its transmembrane synthetic enzyme, hyaluronan synthase (HAS) but recent studies have indicated that the ATP-Binding-Cassette (ABC) transporter, MRP5 contributes to this process. Liberated and cell-associated HA contributes to breast cancer initiation and progression, and therefore the inhibition of ABC transporters and consequently HA transport could provide therapeutic benefit in the treatment of breast cancer. Quantitation of ABC transporter genes, MRP1-5, BCRP and MDR1 were determined in six breast cancer cell lines selected for their differential HA synthetic rates. Low endogenous expression of transporters was detected but no significant correlation existed between ABC transporter and HAS gene expression or HA production. A dose titration of up to ten times the IC(50) of ten small molecule ABC transporter inhibitors did not significantly inhibit HA export in four breast cancer cell lines. Unlike the changes observed after inhibition of HA synthesis by the characterised inhibitor 4-MU, inhibition of ABC transporters did not alter the cell morphology, HA glycocalyx or the intracellular quantity or localisation of HA. Colle...Continue Reading

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Citations

Jun 25, 2014·Applied Microbiology and Biotechnology·Esteban MarcellinLars K Nielsen
Jun 16, 2015·Frontiers in Microbiology·Jochen SchmidBernd Rehm
Feb 22, 2012·Journal of Molecular Biology·Caitlin HubbardJochen Zimmer
Feb 24, 2015·Frontiers in Immunology·Hanna SiiskonenKirsi Rilla
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Mar 3, 2020·Frontiers in Molecular Biosciences·Erik HenkeSüleyman Ergün
Apr 4, 2021·International Journal of Molecular Sciences·Ji HeYan Li

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