MT1-MMP plays an important role in an invasive activity of malignant pleural mesothelioma cell

Our plain-English summary of MT1-MMP plays an important role in an invasive activity of malignant pleural mesothelioma cell, by T. Doi, Y. Maniwa, Y. Tanaka, et al (Experimental and Molecular Pathology, 2011).

The study

• Authors: T. Doi, Y. Maniwa, Y. Tanaka, S. Tane, S. Hashimoto, Y. Ohno, W. Nishio, Y. Nishimura, C. Ohbayashi, Y. Okita, Y. Hayashi, M. Yoshimura
• Journal: Experimental and Molecular Pathology
• Published: 2011;90(1):91-6
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) has a poor prognosis and is a treatment resistant tumor, which is increasing in frequency throughout the world. The poor prognosis is due to the aggressive local invasiveness rather than distant metastasis. In this study, we established a cell line of malignant mesothelioma from a clinical specimen and assessed the relationship between the expression of MT1-MMP and the invasion ability of that line, as well as the cultured cells of several other lines, using the simple method that we created previously. We established a cell line from a clinical specimen from a patient with malignant mesothelioma. We assessed the invasive activities of MPM cells in an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) system that enabled us to visualize cell movements during invasion. To assess the role of MT1-MMP in the invasive activity of MPM cells, we knocked down its expression by RNA interference (RNAi). The invasion assay with DL-CGH revealed that a high expression of MT1-MMP in MPM cells was associated with aggressive invasive activity. The RNAi of MT1-MMP indicated that the expression of MT1-MMP might have a crucial role in the invasiveness of MPM cells. The MT1-MMP expression in MPM cells is related to their capacity for locally aggressive spreading into the pleura and the surrounding tissues, and MT1-MMP should be a suitable molecular target for the suppression of the invasiveness of MPM.

Copyright © 2010 Elsevier Inc. All rights reserved.

In plain English

This laboratory study used human cells grown in dishes. It did not study asbestos exposure or patients' outcomes. The authors grew a new malignant pleural mesothelioma cell line from a tissue sample taken from one patient. They compared it with three purchased mesothelioma cell lines (NCI-H28, NCI-H2452 and MSTO-211H), a lung cancer line (A549) and a fibroblast line (WI38). They measured how much each line made of MT1-MMP, a protein that breaks down the material surrounding cells. They also tested how far the cells spread in a two-layer collagen gel. In the patient's tumor tissue, MT1-MMP was strongly present in tumor cells but not in normal blood-vessel lining cells. The lines with very weak MT1-MMP (A549 and NCI-H28) showed only minimal spread in the gel, while the other lines spread readily. When MT1-MMP was reduced by about 50% in the new mesothelioma line, those cells showed only slight invasion. The authors concluded that MT1-MMP levels are associated with aggressive local spreading and suggested that MT1-MMP could be a treatment target. No numerical measurements of invasion or statistical tests were reported.

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) cell experiment: a new cell line was established from a patient specimen, then several cell lines were compared by protein testing and a collagen gel invasion test, with MT1-MMP reduced by RNA interference
• Who was studied: Cell lines, not people: a mesothelioma cell line the authors established from a clinical specimen from one patient with malignant mesothelioma; three purchased mesothelioma lines, NCI-H28 (pleural effusion), NCI-H2452 (epithelial mesothelioma) and MSTO-211H (biphasic mesothelioma); the A549 lung cancer line; and the WI38 fibroblast line. Work done at Kobe University, Japan.
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the cells' level of the protein MT1-MMP (also called MMP-14), which was reduced in some experiments using RNA interference (siRNA) at a final concentration of 100 nM.
• Main results:
  • The cell line grown from the patient's specimen stained for the mesothelioma markers calretinin, AE1/AE3 and CAM5.2 but not D2-40. The authors took this as confirming the cells were malignant pleural mesothelioma.
  • In the patient's tumor tissue, MT1-MMP was strongly present in tumor cells, especially at their edges. It was not present in normal blood-vessel lining cells.
  • MT1-MMP levels differed by cell line: strong in WI38 and the newly established mesothelioma line, moderate in NCI-H2452 and MSTO-211H, and very weak in A549 and NCI-H28.
  • In the collagen gel test, A549 and NCI-H28 (weak MT1-MMP) showed only minimal invasion into the outer gel layer. The other lines showed a high tendency to invade.
  • RNA interference reduced MT1-MMP protein by about 50% compared with cells given a control siRNA.
  • Cells of the established mesothelioma line with reduced MT1-MMP showed only slight invasion compared with untreated or control-treated cells. The authors reported similar results in WI38 cells but did not show the data.
• The authors' conclusion: The authors suggested that the degree of MT1-MMP expression is associated with the capacity of malignant pleural mesothelioma to spread locally into the pleura and surrounding tissues, and that MT1-MMP will be a molecular target for suppressing its invasion.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Metastasis, Malignant Mesothelioma, Collagen, Pleura.

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