Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients

Our plain-English summary of Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients, by D.J. Burkin, T.M. Fontelonga (The Journal of Pathology, 2015).

The study

• Authors: D.J. Burkin, T.M. Fontelonga
• Journal: The Journal of Pathology
• Published: 2015;237(3):282-4
• Type of article: Comment
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is a disease of pleural cells lining the lungs which is often caused by exposure to asbestos. The molecular mechanism(s) that regulate the transformation of pleural mesothelioma cells to a migratory and malignant phenotype are unclear. In recent work published in this journal, Laszlo et al performed a set of elegant experiments to identify a key molecular mechanism that may explain the aggressive nature of this disease. Using patient-derived mesothelioma cells with high versus low migratory activity, the authors conducted a genome-wide expression analysis. They identified a significant reduction in ITGA7 expression only in highly migratory malignant pleural mesothelioma cells and showed that loss of ITGA7 expression was associated with methylation of the promoter. Forced expression of integrin α7 reversed the migratory phenotype of these cells. Finally, the authors identified a strong correlation between ITGA7 expression and patient survival. Together, these results identify expression of integrin α7 as a molecular mechanism for the aggressive migratory transformation of mesothelioma and identify a potentially novel diagnostic and therapeutic target.

Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

In plain English

This article was an invited commentary, not a new study. The authors described a separate study by Laszlo and colleagues, published in the same journal, on malignant pleural mesothelioma cells taken from patients. Asbestos exposure was not studied; the commentary mentioned asbestos only as a frequent cause of mesothelioma. According to the commentary, Laszlo and colleagues grouped the patients' cells by how well they moved in cell culture. They found 139 genes expressed differently between the low- and high-motility groups, and significantly reduced activity of the ITGA7 gene, which makes a protein called integrin α7, in the high-motility cells. That study reported hypermethylation, a chemical change, of the gene's control region in those cells, and found that restoring integrin α7 reduced cell movement. ITGA7 hypermethylation was reported to correlate strongly with poor outcomes in patients. The commentary gave no patient numbers or survival figures for that study. The authors suggested possible drug approaches and a possible biopsy test based on ITGA7 methylation. They said further research would be required to develop these approaches and reduce possible side effects.

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: Invited commentary on another group's study (Laszlo et al., J Pathol 2015; 237: 203–214); no new data
• Who was studied: As described for the Laszlo et al. study: malignant pleural mesothelioma cells from patients, grouped by how well they migrated in cell culture. The commentary gives no number of patients or cell samples.
• Exposure: No asbestos exposure was studied. The subject is expression of the ITGA7 gene (integrin α7) in mesothelioma cells. Asbestos is mentioned only as a common cause of the disease.
• Main results:
  • As reported from Laszlo et al.: 139 genes were differentially expressed between low- and high-motility cell groups, and ITGA7 transcript was significantly reduced in the high-motility group
  • As reported from Laszlo et al.: the ITGA7 promoter region was hypermethylated in high-motility malignant pleural mesothelioma cells
  • As reported from Laszlo et al.: forcing ITGA7 expression and restoring integrin α7 inhibited cell migration
  • As reported from Laszlo et al.: ITGA7 hypermethylation strongly correlated with poor prognostic outcomes in patients. The commentary gives no numbers.
• The authors' conclusion: The commentators suggested that increasing integrin α7, possibly combined with drugs that inhibit methyltransferases, could be a therapeutic option. They also suggested that a biopsy test of ITGA7 promoter methylation might be developed to monitor disease progression.
• Limitations the authors state:
  • The commentators said further research is needed to develop the proposed treatment approaches and reduce unwanted side effects
  • The commentators noted that drugs targeting ITGA7 transcription are unlikely to work because the promoter is hypermethylated, and that off-target effects in other tissues may be a problem

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: Mesothelioma, Pleural Mesothelioma.

Related studies

• Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma — V. Laszlo, M.A. Hoda, et al. (2015)
• CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome — E. Ortolan, A. Giacomino, et al. (2014)
• Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation — S. Takeuchi, K. Fukuda, et al. (2017)
• Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival — I. Stamenkovic, Q. Yu (2010)
• 3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells — E. Buommino, I. Paoletti, et al. (2010)
• Overexpression of activin-A and -B in malignant mesothelioma - attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth — J.A. Tamminen, M. Yin, et al. (2015)

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