Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling
| Autor: | Darlene Dixon, Yitang Yan, Kevin Gerrish, Rick Fannin, Michael J. Dykstra, Jingli Liu, Erica L. Scappini, Charles J. Tucker, Arianna Lawrence |
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| Rok vydání: | 2021 |
| Předmět: |
MMP1
MMP10 Uterine fibroids cadmium extracellular matrix proliferation Cell Biochemistry Extracellular matrix TGFB1 signaling Transforming Growth Factor beta Cell Line Tumor Genetics medicine NanoString Humans Molecular Biology Research Articles Uterine leiomyoma metallohormone Leiomyoma uterine leiomyoma Chemistry medicine.disease female genital diseases and pregnancy complications uterine fibroid cells medicine.anatomical_structure Cell culture Uterine Neoplasms Cancer research Female Biotechnology Signal Transduction Research Article |
| Zdroj: | The FASEB Journal |
| ISSN: | 1530-6860 |
| Popis: | The heavy metal Cadmium (Cd), a widespread environmental contaminant, poses serious hazards to human health and is considered a metallohormone and carcinogen. In women with uterine fibroids, there is a significant association between blood Cd levels and increased fibroid tumor size. The aim of this study was to determine if benign human uterine leiomyoma (fibroid) cells could be malignantly transformed in vitro by continuous Cd exposure and, if so, explore a molecular mechanism by which this could occur. We found when fibroid cells were exposed to 10 µM CdCl2 for 8 weeks, a robust and fast‐growing Cd‐Resistant Leiomyoma (CR‐LM) cell culture was established. The CR‐LM cells formed viable colonies in soft agar and had increased cytoplasmic glycogen aggregates, enhanced cell motility, a higher percentage of cells in G2/M phase, and increased expression of the proliferation marker Ki‐67. NanoString analysis showed downregulation of genes encoding for extracellular matrix (ECM) components, such as collagens, fibronectins, laminins, and SLRP family proteins, whereas genes involved in ECM degradation (MMP1, MMP3, and MMP10) were significantly upregulated. A volcano plot showed that the top differentially genes favored cancer progression. Functional analysis by ingenuity pathway analysis predicted a significant inhibition of TGFB1 signaling, leading to enhanced proliferation and attenuated fibrosis. Prolonged Cd exposure altered phenotypic characteristics and dysregulated genes in fibroid cells predicative of progression towards a cancer phenotype. Therefore, continuous Cd exposure alters the benign characteristics of fibroid cells in vitro, and Cd exposure could possibly pose a health hazard for women with uterine fibroids. |
| Databáze: | OpenAIRE |
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