Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells

Our plain-English summary of Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells, by H. Yamazaki, M. Naito, F.I. Ghani, et al (Biochemical and Biophysical Research Communications, 2012).

The study

• Authors: H. Yamazaki, M. Naito, F.I. Ghani, N.H. Dang, S. Iwata, C. Morimoto
• Journal: Biochemical and Biophysical Research Communications
• Published: 2012;419(3):529-36
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSC properties in MM cells. Among these markers, we focused on two: CD24, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERK by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy.

Copyright © 2012 Elsevier Inc. All rights reserved.

In plain English

This laboratory study used three human malignant mesothelioma cell lines: JMN (sarcomatoid), H226 and Meso-1 (both epithelioid). It did not study asbestos exposure or patients. The authors examined two cell-surface markers, CD24 and CD26, that their earlier work had linked to 'cancer stem cell' properties. They sorted cells by marker and reduced marker expression with shRNA, by more than 90% in Meso-1. In JMN, cells positive for either marker were more invasive; in H226, CD24-positive cells were. Reducing either marker slowed growth in both lines. In Meso-1, where the two markers occurred independently, CD24 was associated with resistance to daunomycin and etoposide and with growth, while CD26 was associated with asymmetric cell division and invasion. The gene IGFBP7 was more active in marker-positive or control cells in all four comparisons, by 1.9-fold to 27.3-fold. In Meso-1, ERK2 activation after EGF stimulation was suppressed in CD26-negative cells, while CD24 sorting or knockdown did not affect it. The authors concluded that CD24 and CD26 share and regulate various cancer stem cell functions and may give new clues to treatment approaches.

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: in vitro laboratory study of human malignant mesothelioma cell lines (cell sorting, shRNA knockdown, drug, invasion, growth, microarray and signaling experiments)
• Who was studied: three human malignant mesothelioma cell lines: JMN (sarcomatoid), H226 (epithelioid) and Meso-1 (epithelioid); no patients
• Exposure: No asbestos exposure was studied. The experimental factors were expression of the cell-surface markers CD24 and CD26, examined by cell sorting and by shRNA knockdown. Cells were also tested with 13 anti-cancer drugs and with EGF stimulation.
• Main results:
  • In Meso-1 cells, CD26-positive cells regenerated both positive and negative populations, while CD26-negative cells hardly regenerated CD26-positive cells. The authors interpreted this as asymmetric cell division potential.
  • All three cell lines were resistant to cisplatin. Daunomycin and etoposide increased the proportion of CD24-positive cells, indicating these cells were relatively drug-resistant. The proportion of CD26-positive Meso-1 cells did not increase.
  • shRNA reduced CD24 and CD26 expression by more than 90% in Meso-1 compared with a non-targeting control. Expression was reduced at similar levels in JMN and H226, but those data were not shown.
  • CD24-positive and CD26-positive JMN cells and CD24-positive H226 cells were significantly more invasive than marker-negative cells. In H226, CD26 was expressed homogeneously.
  • In Meso-1, CD26-positive cells were more invasive than CD26-negative cells, but no difference in invasion was seen between CD24-positive and CD24-negative cells.
  • Knocking down CD24 or CD26 significantly slowed growth in JMN and H226. In Meso-1, only CD24 knockdown slowed growth; CD26 knockdown did not.
  • IGFBP7 was up-regulated in all four comparisons: 2.5-fold in JMN CD24-positive cells, 3.3-fold in H226 CD24-positive cells, 27.3-fold in Meso-1 CD24+/CD26+ cells, and 1.9-fold in Meso-1 control versus CD24-shRNA cells
  • In EGF-stimulated Meso-1 cells, phosphorylation of ERK2 was significantly suppressed at 5 minutes in CD26-negative cells and in CD26-knockdown cells. ERK1/2 phosphorylation was not affected in the CD24 experiments.
• The authors' conclusion: The authors concluded that CD24 and CD26 share and regulate various cellular functions of cancer stem cells and may give new clues to cancer-stem-cell-oriented treatment of malignant mesothelioma. They added that the relative expression pattern of the two markers should be taken into account in each clinical case.

Topics

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

Medical terms in this study, explained in our Lexicon: STEM, Malignant Mesothelioma, Prognosis.

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• Multipotent cancer stem cells derived from human malignant peritoneal mesothelioma promote tumorigenesis — S. Varghese, R. Whipple, et al. (2012)
• Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed — L. Cortes-Dericks, G.L. Carboni, et al. (2010)
• Characterization of side population cells in human malignant mesothelioma cell lines — K. Kai, S. D'Costa, et al. (2010)
• Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis — C.W. Menges, Y. Kadariya, et al. (2014)

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