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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| Veröffentlicht in: | Frontiers in medicine Jg. 8; S. 746532 |
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| Abstract | 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. |
|---|---|
| AbstractList | Zinc (Zn) accumulates in breast cancer tumors compared to adjacent healthy tissue. Clinical samples of breast cancer tissue show light Zn isotopic compositions (δ66Zn) 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 (Δ66Znuptake) and cell efflux (Δ66Znefflux) 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 (Δ66Znuptake = +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 (Δ66Znefflux = −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. 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. Zinc (Zn) accumulates in breast cancer tumors compared to adjacent healthy tissue. Clinical samples of breast cancer tissue show light Zn isotopic compositions (δ Zn) relative to healthy tissue. The underlying mechanisms causing such effects are unknown. To investigate if the isotopic discrimination observed for breast cancer tissue samples can be reproduced , 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 Zn ) and cell efflux (Δ Zn ) using a drip-flow reactor to enable comparison with the environment. The MDA-MB-231 cell line analyses show Zn isotopic fractionations in an opposite direction to those observed for breast cancer tissue. Uptake of isotopically heavy Zn (Δ Zn = +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 Zn = -0.35 ± 0.06‰). The difference in Zn isotope fractionation observed between MDA-MB-231 cell line experiments and 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 and Zn isotope fractionation. Zinc (Zn) accumulates in breast cancer tumors compared to adjacent healthy tissue. Clinical samples of breast cancer tissue show light Zn isotopic compositions (δ66Zn) 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 (Δ66Znuptake) and cell efflux (Δ66Znefflux) 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 (Δ66Znuptake = +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 (Δ66Znefflux = -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.Zinc (Zn) accumulates in breast cancer tumors compared to adjacent healthy tissue. Clinical samples of breast cancer tissue show light Zn isotopic compositions (δ66Zn) 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 (Δ66Znuptake) and cell efflux (Δ66Znefflux) 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 (Δ66Znuptake = +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 (Δ66Znefflux = -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. |
| Author | Schilling, Kathrin Larner, Fiona Sheldon, Helen Schofield, Christopher J. Harris, Adrian L. Halliday, Alex N. Haider, Syed |
| AuthorAffiliation | 5 The Breast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research , London , United Kingdom 4 Department of Chemistry, University of Oxford , Oxford , United Kingdom 1 Lamont Doherty Earth Observatory, Columbia University , Palisades, NY , United States 2 Department of Medical Oncology, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , United Kingdom 3 Department of Earth Sciences, University of Oxford , Oxford , United Kingdom |
| AuthorAffiliation_xml | – name: 5 The Breast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research , London , United Kingdom – name: 4 Department of Chemistry, University of Oxford , Oxford , United Kingdom – name: 3 Department of Earth Sciences, University of Oxford , Oxford , United Kingdom – name: 1 Lamont Doherty Earth Observatory, Columbia University , Palisades, NY , United States – name: 2 Department of Medical Oncology, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , United Kingdom |
| Author_xml | – sequence: 1 givenname: Kathrin surname: Schilling fullname: Schilling, Kathrin – sequence: 2 givenname: Adrian L. surname: Harris fullname: Harris, Adrian L. – sequence: 3 givenname: Alex N. surname: Halliday fullname: Halliday, Alex N. – sequence: 4 givenname: Christopher J. surname: Schofield fullname: Schofield, Christopher J. – sequence: 5 givenname: Helen surname: Sheldon fullname: Sheldon, Helen – sequence: 6 givenname: Syed surname: Haider fullname: Haider, Syed – sequence: 7 givenname: Fiona surname: Larner fullname: Larner, Fiona |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35127740$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_microc_2022_108033 crossref_primary_10_3389_fphar_2025_1543166 crossref_primary_10_1093_mtomcs_mfac038 crossref_primary_10_3390_nu15071703 crossref_primary_10_1007_s00339_023_06521_4 crossref_primary_10_1016_j_earscirev_2025_105185 crossref_primary_10_1016_j_jtemb_2025_127733 crossref_primary_10_1016_j_jtemb_2023_127246 |
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| Keywords | ZIP breast cancer efflux uptake Zn isotopes MDA-MB-231 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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 |
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| SubjectTerms | 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 |
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| Title | Investigations on Zinc Isotope Fractionation in Breast Cancer Tissue Using in vitro Cell Culture Uptake-Efflux Experiments |
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