Investigations on Zinc Isotope Fractionation in Breast Cancer Tissue Using 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 (δZn) 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 (ΔZn) and cell efflux (ΔZn) 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 (ΔZn = +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 (ΔZn = -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.