Investigations on Zinc Isotope Fractionation in Breast Cancer Tissue Using in vitro Cell Culture Uptake-Efflux Experiments

Zinc (Zn) accumulates in breast cancer tumors compared to adjacent healthy tissue. Clinical samples of breast cancer tissue show light Zn isotopic compositions (δ 66 Zn) relative to healthy tissue. The underlying mechanisms causing such effects are unknown. To investigate if the isotopic discriminat...

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Published in:Frontiers in medicine Vol. 8; p. 746532
Main Authors: Schilling, Kathrin, Harris, Adrian L., Halliday, Alex N., Schofield, Christopher J., Sheldon, Helen, Haider, Syed, Larner, Fiona
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media SA 20.01.2022
Frontiers Media S.A
Subjects:
Acids
Biofilms
Biomarkers
Breast cancer
Cell growth
Copper
Effluents
efflux
Experiments
Isotopes
Ligands
Light
MDA-MB-231
Medicine
Penicillin
Proteins
Tissues
uptake
ZIP
Zn isotopes
United Kingdom > UK
United States > US
ZIP
breast cancer
efflux
uptake
Zn isotopes
MDA-MB-231
ISSN:2296-858X, 2296-858X
Online Access:Get full text
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Summary:Zinc (Zn) accumulates in breast cancer tumors compared to adjacent healthy tissue. Clinical samples of breast cancer tissue show light Zn isotopic compositions (δ 66 Zn) relative to healthy tissue. The underlying mechanisms causing such effects are unknown. To investigate if the isotopic discrimination observed for in vivo breast cancer tissue samples can be reproduced in vitro , we report isotopic data for Zn uptake-efflux experiments using a human breast cancer cell line. MDA-MB-231 cell line was used as a model for triple receptor negative breast cancer. We determined Zn isotope fractionation for Zn cell uptake (Δ 66 Zn uptake ) and cell efflux (Δ 66 Zn efflux ) using a drip-flow reactor to enable comparison with the in vivo environment. The MDA-MB-231 cell line analyses show Zn isotopic fractionations in an opposite direction to those observed for in vivo breast cancer tissue. Uptake of isotopically heavy Zn (Δ 66 Zn uptake = +0.23 ± 0.05‰) is consistent with transport via Zn transporters (ZIPs), which have histidine-rich binding sites. Zinc excreted during efflux is isotopically lighter than Zn taken up by the cells (Δ 66 Zn efflux = −0.35 ± 0.06‰). The difference in Zn isotope fractionation observed between in vitro MDA-MB-231 cell line experiments and in vivo breast tissues might be due to differences in Zn transporter levels or intercellular Zn storage (endoplasmic reticulum and/or Zn specific vesicles); stromal cells, such as fibroblasts and immune cells. Although, additional experiments using other human breast cancer cell lines (e.g., MCF-7, BT-20) with varying Zn protein characteristics are required, the results highlight differences between in vitro and in vivo Zn isotope fractionation.
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Reviewed by: Frederic Moynier, UMR7154 Institut de Physique du Globe de Paris (IPGP), France; Lucie Sauzéat, Université Clermont Auvergne, France
Edited by: Elham Sajjadi, University of Milan, Italy
This article was submitted to Translational Medicine, a section of the journal Frontiers in Medicine
ISSN:2296-858X
2296-858X
DOI:10.3389/fmed.2021.746532