CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells

Our plain-English summary of CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells, by E. Komiya, K. Ohnuma, H. Yamazaki, et al (Biochemical and Biophysical Research Communications, 2014).

The study

• Authors: E. Komiya, K. Ohnuma, H. Yamazaki, R. Hatano, S. Iwata, T. Okamoto, N.H. Dang, T. Yamada, C. Morimoto
• Journal: Biochemical and Biophysical Research Communications
• Published: 2014;447(4):609-15
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM.

Copyright © 2014 Elsevier Inc. All rights reserved.

In plain English

This was a laboratory study using two human malignant pleural mesothelioma cell lines, JMN and MSTO-211H. It did not study people or asbestos exposure. The authors examined CD26, a protein on the cell surface, and periostin, a protein the cells release. When CD26 was reduced in JMN cells, which naturally carry it, the cells made significantly less periostin. MSTO-211H cells given full-length CD26 made significantly more periostin than cells given an empty vector or a version of CD26 lacking its own inner (cytoplasmic) tail. Lowering CD26 also reduced activated Src, a signaling protein, and reduced the amount of a factor called Twist1 in the cell nucleus. A chemical that blocks Src (PP2) reduced Twist1 in the nucleus and reduced periostin production. Blocking periostin reduced the cells' movement and invasion through filters in laboratory chambers, while adding periostin increased them. The authors concluded that CD26 raises periostin through Src and Twist1, which enhances migration and invasion of these cells. They said the findings may lead to new treatment strategies.

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
• Who was studied: Two human malignant pleural mesothelioma cell lines: MSTO-211H (from the American Type Culture Collection) and JMN (which expresses CD26 naturally); no human subjects
• Exposure: No asbestos exposure was studied. The experiments changed CD26 levels: CD26 was reduced in JMN cells, and MSTO-211H cells were given full-length CD26, a CD26–CD10 chimeric receptor lacking CD26's cytoplasmic tail, or an empty vector. The experiments also reduced or added periostin, and treated cells with the Src inhibitor PP2.
• Main results:
  • In JMN cells with CD26 knocked down, periostin mRNA and secreted periostin protein were significantly decreased.
  • In MSTO-211H cells, periostin mRNA and protein were significantly increased in cells with full-length CD26 compared with cells carrying the CD26–CD10 chimera or empty vector.
  • CD26 knockdown in JMN cells decreased phosphorylated (activated) Src and nuclear Twist1. Full-length CD26 in MSTO-211H cells increased both.
  • In cells with full-length CD26, CD26 and Src gathered in lipid raft fractions of the membrane. In cells with the CD26–CD10 chimera, phosphorylated Src was not observed.
  • The Src inhibitor PP2 reduced Twist1 nuclear translocation and significantly decreased periostin mRNA and secretion in JMN and MSTO-CD26WT cells.
  • Knocking down periostin significantly decreased migration and invasion of JMN and MSTO-CD26WT cells.
  • Adding periostin to the medium increased migration and invasion of MSTO-Mock and MSTO-CD26/10Chi cells.
• The authors' conclusion: The authors concluded that CD26-associated upregulation of periostin in MPM cells results from nuclear translocation of Twist1 following CD26-mediated Src activation, and that increased periostin secretion enhances migration and invasion of MPM cells. They suggested this may lead to novel therapeutic strategies.

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: Pleural Mesothelioma, Pleura, Asbestos Exposure, Prognosis, Translocation.

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• Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update — L. Morra, H. Moch (2011)
• Identification of cancer stem cell markers in human malignant mesothelioma cells — F.I. Ghani, H. Yamazaki, et al. (2011)
• AHNAK is highly expressed and plays a key role in cell migration and invasion in mesothelioma — H. Sudo, A.B. Tsuji, et al. (2014)
• Deficiency of Fyn protein is prerequisite for apoptosis induced by Src family kinase inhibitors in human mesothelioma cells — R. Eguchi, S. Kubo, et al. (2012)
• Clinical significance of soluble CD26 in malignant pleural mesothelioma — N. Fujimoto, K. Ohnuma, et al. (2014)

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