Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling [CanPath]
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PROVIDER: PRJNA740336 | ENA |
REPOSITORIES: ENA
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Project description:Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling
| PRJNA740338 | ENA
Project description:Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling [CanProg]
| PRJNA740341 | ENA
Project description:In our lab, Cadmium treatment of human fibroid cells induced a cancer phenotype and altered glycogen metabolism. In this study we treated fibroid cells with cadmium continuously for 2 or 6 months. Cancer progression and pathway gene expression were investigated using NanoString Technologies.
2021-10-29 | GSE178789 | GEO
Project description:In our lab, Cadmium treatment of human fibroid cells induced a cancer phenotype and altered glycogen metabolism. In this study we treated fibroid cells with cadmium continuously for 2 or 6 months. Cancer progression and pathway gene expression were investigated using NanoString Technologies.
2021-10-29 | GSE178786 | GEO
Project description: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.
| S-EPMC8284923 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-29 | GSE178790 | GEO
Project description: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 fibroid tumor size. The aim of this study was to determine if benign uterine 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) culture was established. The CR-LM cells showed the ability to form viable colonies in soft agar, increased 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 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 direction of expression changes of the top differentially genes favored cancer progression. Functional analysis by IPA predicted a significant inhibition of TGFβ 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 exposures changes the phenotype of benign fibroid cells in vitro and could possibly pose a health risk for women with uterine fibroids.
2023-11-13 | GSE161454 | GEO
Project description: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 fibroid tumor size. The aim of this study was to determine if benign uterine 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) culture was established. The CR-LM cells showed the ability to form viable colonies in soft agar, increased 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 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 direction of expression changes of the top differentially genes favored cancer progression. Functional analysis by IPA predicted a significant inhibition of TGFβ 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 exposures changes the phenotype of benign fibroid cells in vitro and could possibly pose a health risk for women with uterine fibroids.
2023-11-13 | GSE161455 | GEO
Project description:The aim of this study is to compare the expression patterns of tyrosine kinases and their ligand activators between matched myometrium and leiomyoma tissues. For this, total RNA samples extracted from 42 pairs of matched fibroid and adjacent myometrial tissues were hybridized to a set of 840 customized oligonucleotide microarrays to compare the expression profiles of 244 selected human genes including all 90 tyrosine kinases and 103 ligands. Among the 244 genes surveyed, 38 were found to be differentially expressed between pairs of myometrium and fibroid tissues. Clustering analysis of the expression ratios of these 38 genes from 42 pairs of samples has led to the subdivision of fibroid samples into three groups, based on the expression ratios of two peptide ligands, CYR61 and EFNA4. Real-time quantitative RT-PCR measurements of additional 32 pairs of samples further confirmed the existence of these three groups of fibroid samples. In conclusion, peptide ligand activators of protein tyrosine kinases are differentially expressed between myometrium and fibroid tissues. This finding supports the notion that tyrosine kinases may be exploited as medical targets to treat symptomatic fibroids without surgical intervention.  This study has been accomplished with 42 patients fibroid specimen and their matched myometrium, each pair of specimen has been repeated at least 3 times.
2009-11-20 | E-GEOD-19127 | biostudies-arrayexpress
Project description:Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and from matched myometrial (MF) and fibroid (F) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1,169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs M were not found in the F vs MF, which are likely understudied in the pathogenesis of uterine fibroids. These results suggest that the transcriptome of MF tissues are different from non-diseased myometrial tissues. Many dysregulated genes were not included in the F vs MF DEGs and may contain key genes for future investigations suggesting that fibroid studies should consider using not only matched myometrium but also non-diseased myometrium as the control.
2021-03-21 | GSE169255 | GEO