Cargando…

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

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 CdCl(2)...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Yitang, Shi, Min, Fannin, Rick, Yu, Linda, Liu, Jingli, Castro, Lysandra, Dixon, Darlene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031958/
https://www.ncbi.nlm.nih.gov/pubmed/35453667
http://dx.doi.org/10.3390/biomedicines10040917
_version_ 1784692521357541376
author Yan, Yitang
Shi, Min
Fannin, Rick
Yu, Linda
Liu, Jingli
Castro, Lysandra
Dixon, Darlene
author_facet Yan, Yitang
Shi, Min
Fannin, Rick
Yu, Linda
Liu, Jingli
Castro, Lysandra
Dixon, Darlene
author_sort Yan, Yitang
collection PubMed
description 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 CdCl(2) 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.
format Online
Article
Text
id pubmed-9031958
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90319582022-04-23 Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis Yan, Yitang Shi, Min Fannin, Rick Yu, Linda Liu, Jingli Castro, Lysandra Dixon, Darlene Biomedicines Article 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 CdCl(2) 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. MDPI 2022-04-16 /pmc/articles/PMC9031958/ /pubmed/35453667 http://dx.doi.org/10.3390/biomedicines10040917 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yan, Yitang
Shi, Min
Fannin, Rick
Yu, Linda
Liu, Jingli
Castro, Lysandra
Dixon, Darlene
Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
title Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
title_full Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
title_fullStr Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
title_full_unstemmed Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
title_short Prolonged Cadmium Exposure Alters Migration Dynamics and Increases Heterogeneity of Human Uterine Fibroid Cells—Insights from Time Lapse Analysis
title_sort prolonged cadmium exposure alters migration dynamics and increases heterogeneity of human uterine fibroid cells—insights from time lapse analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031958/
https://www.ncbi.nlm.nih.gov/pubmed/35453667
http://dx.doi.org/10.3390/biomedicines10040917
work_keys_str_mv AT yanyitang prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis
AT shimin prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis
AT fanninrick prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis
AT yulinda prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis
AT liujingli prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis
AT castrolysandra prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis
AT dixondarlene prolongedcadmiumexposurealtersmigrationdynamicsandincreasesheterogeneityofhumanuterinefibroidcellsinsightsfromtimelapseanalysis