PUBLICATION
The Effects of Perfluorooctanoic Acid on Breast Cancer Metastasis Depend on the Phenotypes of the Cancer Cells: An in vivo Study with Zebrafish Xenograft Model
- Authors
- Huang, C., Murgulet, I., Liu, L., Zhang, M., Garcia, K., Martin, L., Xu, W.
- ID
- ZDB-PUB-240919-5
- Date
- 2024
- Source
- Environmental pollution (Barking, Essex : 1987) 362: 124975 (Journal)
- Registered Authors
- Keywords
- Breast cancer, Per- and polyfluorinated substances, Perfluorooctanoic acid, Preadipocytes, Zebrafish xenograft model
- MeSH Terms
-
- Fluorocarbons*/toxicity
- Caprylates*/toxicity
- Cadherins/genetics
- Cadherins/metabolism
- Zebrafish*
- MCF-7 Cells
- Neoplasm Metastasis
- Breast Neoplasms*
- Cell Movement/drug effects
- Humans
- Cell Proliferation/drug effects
- Animals
- Cell Line, Tumor
- Phenotype
- Female
- PubMed
- 39293659 Full text @ Environ. Pollut.
Citation
Huang, C., Murgulet, I., Liu, L., Zhang, M., Garcia, K., Martin, L., Xu, W. (2024) The Effects of Perfluorooctanoic Acid on Breast Cancer Metastasis Depend on the Phenotypes of the Cancer Cells: An in vivo Study with Zebrafish Xenograft Model. Environmental pollution (Barking, Essex : 1987). 362:124975.
Abstract
Per- and polyfluorinated substances (PFAS) have been associated with numerous human diseases. Recent in vitro studies have implicated the association of PFAS with an increased risk of breast cancer in humans. This study aimed to assess the toxic effects of PFAS during the development of human breast cancer using a zebrafish xenograft model. Perfluorooctanoic acid (PFOA) was used as a PFAS chemical of interest for this study. Two common breast cancer cell lines, MCF-7 and MDA-MB-231, were used to represent the diversity of breast cancer phenotypes. Human preadipocytes were co-implanted with the breast cancer cells into the zebrafish embryos to optimize the microenvironment for tumor cells in vivo. With this modified model, we evaluated the potential effects of the PFOA on the metastatic potential of the two types of breast cancer cells. The presence of human preadipocytes resulted in an enhancement to the metastasis progress of the two types of cells, including the promotion of cell in vivo migration and proliferation, and the increased expression levels of metastatic biomarkers. The enhancement of MCF-7 proliferation by preadipocytes was observed after 2 days post injection (dpi) while the increase of MDA-MB-231 proliferation was seen after 6 dpi. The breast cancer metastatic biomarkers, cadherin 1 (cdh1), and small breast epithelial mucin (sbem) genes demonstrated significant down- and upregulations respectively, by the co-injection of preadipocytes. In the optimized xenograft model, the PFOA consistently promoted cell proliferation and migration and altered the metastatic biomarker expression in MCF-7, which suggested a metastatic effect of PFOA on MCF-7. However, those effects were not consistently observed in MDA-MB-231. The presence of the preadipocytes in the xenograft model may provide a necessary microenvironment for the progress of tumor cells in zebrafish embryos. The finding suggested that the impacts of PFOA exposure on different phenotypes of breast cancers may differ.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping