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Article

Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis

1
Molecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Durham, NC 27709, USA
2
Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Durham, NC 27709, USA
3
Molecular Genomics Core Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Durham, NC 27709, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Kenichi Suda
Biomedicines 2022, 10(4), 917; https://doi.org/10.3390/biomedicines10040917
Received: 19 February 2022 / Revised: 3 April 2022 / Accepted: 5 April 2022 / Published: 16 April 2022
(This article belongs to the Special Issue Advanced Research in Cell Motility)
Cadmium (Cd) is one of the most prevalent environmental heavy metal contaminants and is considered an endocrine disruptor and carcinogen. In women with uterine fibroids, there is a correlation between blood Cd levels and fibroid tumor size. In this study, fibroid cells were exposed to 10 µM CdCl2 for 6 months and a fast-growing Cd-Resistant Leiomyoma culture, termed CR-LM6, was recovered. To characterize the morphological and mechanodynamic features of uterine fibroid cells associated with prolonged Cd exposure, we conducted time lapse imaging using a Zeiss confocal microscope and analyzed data by Imaris and RStudio. Our experiments recorded more than 64,000 trackable nuclear surface objects, with each having multiple parameters such as nuclear size and shape, speed, location, orientation, track length, and track straightness. Quantitative analysis revealed that prolonged Cd exposure significantly altered cell migration behavior, such as increased track length and reduced track straightness. Cd exposure also significantly increased the heterogeneity in nuclear size. Additionally, Cd significantly increased the median and variance of instantaneous speed, indicating that Cd exposure results in higher speed and greater variation in motility. Profiling of mRNA by NanoString analysis and Ingenuity Pathway Analysis (IPA) strongly suggested that the direction of gene expression changes due to Cd exposure enhanced cell movement and invasion. The altered expression of extracellular matrix (ECM) genes such as collagens, matrix metallopeptidases (MMPs), secreted phosphoprotein 1 (SPP1), which are important for migration contact guidance, may be responsible for the greater heterogeneity. The significantly increased heterogeneity of nuclear size, speed, and altered migration patterns may be a prerequisite for fibroid cells to attain characteristics favorable for cancer progression, invasion, and metastasis. View Full-Text
Keywords: cadmium; fibroid; migration; time lapse; Ingenuity Pathway Analysis; straightness; heterogeneity; variance; carcinogenesis cadmium; fibroid; migration; time lapse; Ingenuity Pathway Analysis; straightness; heterogeneity; variance; carcinogenesis
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MDPI and ACS Style

Yan, Y.; Shi, M.; Fannin, R.; Yu, L.; Liu, J.; Castro, L.; Dixon, D. Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis. Biomedicines 2022, 10, 917. https://doi.org/10.3390/biomedicines10040917

AMA Style

Yan Y, Shi M, Fannin R, Yu L, Liu J, Castro L, Dixon D. Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis. Biomedicines. 2022; 10(4):917. https://doi.org/10.3390/biomedicines10040917

Chicago/Turabian Style

Yan, Yitang, Min Shi, Rick Fannin, Linda Yu, Jingli Liu, Lysandra Castro, and Darlene Dixon. 2022. "Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis" Biomedicines 10, no. 4: 917. https://doi.org/10.3390/biomedicines10040917

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