Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis

Our plain-English summary of Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis, by T. Plönes, M. Fischer, K. Höhne, et al (Pathology Oncology Research, 2017).

The study

• Authors: T. Plönes, M. Fischer, K. Höhne, H. Sato, J. Müller-Quernheim, G. Zissel
• Journal: Pathology Oncology Research
• Published: 2017;23(4):723-730
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.

In plain English

This was a laboratory study of two human malignant pleural mesothelioma cell lines, MSTO-211H and NCI-H2052. It did not study people or asbestos exposure. The authors used small interfering RNA (siRNA) to lower levels of a protein called WT1. They compared these cells with untreated cells and with cells given a scrambled control siRNA. In MSTO cells, cell growth fell significantly (optical density 1.2 untreated, 0.8 scrambled, 0.6 knockdown). For H2052 cells, the text reports a significant drop compared with untreated cells, but the figure legend says the drop did not reach significance. Movement of cells toward a growth factor fell in both lines, but not significantly. Invasion through a gel barrier fell significantly in both lines. In MSTO cells, for example, it fell from 769 cells per view with scrambled siRNA to 383 with knockdown. Resistance to the cancer drug cisplatin fell significantly only in MSTO cells. The authors concluded that WT1 may be an interesting treatment target. They noted that the knockdown reduces WT1 only for a while.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human mesothelioma cell lines using siRNA knockdown of WT1
• Who was studied: Two human mesothelioma cell lines, NCI-H2052 and MSTO-211H; no human subjects
• Exposure: No asbestos exposure was studied. Cells were treated with siRNA against WT1 (compared with scrambled siRNA and untreated cells). Chemoresistance was tested with cisplatin.
• Main results:
  • MSTO cells: proliferation (BrdU, optical density) was 1.2 in untreated cells, 0.8 with scrambled siRNA and 0.6 with WT1 knockdown; p less than 0.02
  • H2052 cells: proliferation was 0.21 untreated, 0.21 scrambled and 0.16 knockdown. The text gives p less than 0.04 (untreated vs knockdown), but the figure legend says this reduction did not reach significance.
  • Chemotaxis (mean cells per view) was 97, 75 and 39 in H2052 and 21, 17 and 12 in MSTO (untreated, scrambled, knockdown). The reduction was not statistically significant.
  • Invasion in H2052 was 149 cells per view untreated, 53 scrambled and 18 knockdown; significant (p less than 0.03) only for scrambled vs knockdown
  • Invasion in MSTO was 926 cells per view untreated, 769 scrambled and 383 knockdown; p less than 0.03 for untreated vs knockdown and for scrambled vs knockdown
  • Cisplatin chemoresistance in MSTO was 0.71 untreated, 0.66 scrambled and 0.62 knockdown; per the figure legend, p less than 0.01 for scrambled vs knockdown only
  • Cisplatin chemoresistance in H2052 was 0.93 untreated, 0.97 scrambled and 0.81 knockdown; not statistically significant
• The authors' conclusion: The authors concluded that WT1 plays a key role in several features related to MPM treatment and may be an interesting treatment target.
• Limitations the authors state:
  • It is unclear whether the histological subtypes of mesothelioma are influenced by epithelial-to-mesenchymal transition
  • siRNA knockdown reduces WT1 expression only temporarily

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Wilms Tumor 1 (WT-1), Mesothelioma, Pleural Mesothelioma, Pleura, Asbestos Exposure, Median Survival, Malignant Mesothelioma.

Related studies

• Wilms tumor 1/cytokeratin dual-color immunostaining reveals distinctive staining patterns in metastatic melanoma, metastatic carcinoma, and mesothelial cells in pleural fluids: an effective first-line test for the workup of malignant effusions — J.R. Conner, E.S. Cibas, et al. (2014)
• APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis — V. Ramundo, G. Zanirato, et al. (2023)
• Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma — S. Cedrés, M.A. Montero, et al. (2014)
• Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells — Y.J. Lee, I.S. Hwang, et al. (2014)
• Epithelial-mesenchymal transition in malignant mesothelioma — A. Fassina, R. Cappellesso, et al. (2012)
• Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway — M. Polimeni, G.R. Gulino, et al. (2016)

Browse more research in Pathology Oncology Research, or return to medical research.