Identification of cancer stem cell markers in human malignant mesothelioma cells

Our plain-English summary of Identification of cancer stem cell markers in human malignant mesothelioma cells, by F.I. Ghani, H. Yamazaki, S. Iwata, et al (Biochemical and Biophysical Research Communications, 2011).

The study

• Authors: F.I. Ghani, H. Yamazaki, S. Iwata, T. Okamoto, K. Aoe, K. Okabe, Y. Mimura, N. Fujimoto, T. Kishimoto, T. Yamada, C.W. Xu, C. Morimoto
• Journal: Biochemical and Biophysical Research Communications
• Published: 2011;404(2):735-42
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24(+) cells proliferated by asymmetric cell division-like manner. In addition, CD9(+) and CD24(+) cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.

Copyright © 2010 Elsevier Inc. All rights reserved.

In plain English

This laboratory study did not examine asbestos exposure. The authors transplanted 9 surgical malignant mesothelioma samples into immunodeficient (NOD/SCID) mice, and tumors grew from all samples. From these mouse tumors they established 5 new cell lines, TUM1 to TUM5. They then tested 9 mesothelioma cell lines (8 existing lines plus TUM1) for features associated with "cancer stem cells". Six of the 9 lines contained a "side population" making up 1.0% to 21.9% of cells. CD26 was highly expressed in 8 of 9 lines, and CD24 and CD26 expression were correlated in two sarcomatoid lines, JMN and H28. In TUM1, cells high in CD9 or positive for CD24 formed more spheroid colonies. In mice, marker-positive cells generally formed relatively larger tumors, though the authors said the data were statistically insufficient in some cases. Differences were significant for JMN cells positive for both CD24 and CD26 (average tumor weight 0.247 g versus 0.063 g) and for high-CD9 cells from tumor tissue. The authors concluded that side population, CD9, CD24 and CD26 are cancer stem cell markers in mesothelioma and potential treatment targets.

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 study of human mesothelioma cell lines and tumor samples, including mouse transplantation (xenograft) experiments
• Who was studied: 9 human malignant mesothelioma surgical tissue samples, obtained under ethics approval at the University of Tokyo, Okayama Rosai Hospital and Yamaguchi-Ube Medical Center (Japan), transplanted into NOD/SCID mice. Also 9 mesothelioma cell lines (8 existing lines plus the new line TUM1) used for marker analysis.
• Exposure: No asbestos exposure was studied. The study examined stem-cell-related features of mesothelioma cells: side population (SP) cells and the surface markers CD9, CD24, CD26, CD44, CD90 and CD133.
• Main results:
  • Xenograft tumors developed from all 9 surgical samples in mice, between 10 and 29 weeks after transplantation.
  • 6 of the 9 cell lines contained side population cells, ranging from 1.0% to 21.9% of total cells.
  • In cell lines H226 and H2452, only side population cells could regenerate both cell types, which the authors described as asymmetric cell division-like proliferation.
  • Asymmetric cell division-like proliferation of CD24-positive cells occurred only in the JMN and H226 cell lines.
  • CD26 was highly expressed in 8 of 9 cell lines. CD24 and CD26 expression were significantly correlated in the sarcomatoid lines JMN and H28, but showed no clear correlation in the epithelioid lines.
  • In TUM1 cells grown in stem cell medium, CD9-high and CD24-positive cells formed more spheroid colonies than CD9-low and CD24-negative cells.
  • In mice, JMN cells positive for both CD24 and CD26 produced an average tumor weight of 0.247 g, versus 0.063 g for cells negative for both (6 mice each, 8 weeks). The difference was statistically significant (P less than 0.05).
  • In mice, CD9-high cells taken from patient 2's xenograft tumor tissue produced larger tumors than CD9-low cells (3 mice each). Average tumor weights were 0.240 g versus 0.013 g, and 0.290 g versus 0 g in a second experiment with fewer cells. Both differences were statistically significant.
• The authors' conclusion: The authors concluded that SP, CD9, CD24 and CD26 are markers of cancer stem cells in malignant mesothelioma, and that therapy targeting these markers could be a novel treatment approach.
• Limitations the authors state:
  • The authors stated that the transplantation results were statistically insufficient in some cases. Only some marker comparisons reached statistical significance.

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, Neoplasm, Mesothelial Cells, Asbestos Exposure.

Related studies

• Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells — H. Yamazaki, M. Naito, et al. (2012)
• Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in carbon nanotube-driven tumorigenesis — S. Luanpitpong, L. Wang, et al. (2014)
• Clinical significance of soluble CD26 in malignant pleural mesothelioma — N. Fujimoto, K. Ohnuma, et al. (2014)
• CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma — V.J. Amatya, Y. Takeshima, et al. (2013)
• CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells — E. Komiya, K. Ohnuma, et al. (2014)
• CD24: a potential new marker in differentiating malignant mesothelioma from pulmonary adenocarcinoma — D.J. Pinato, P. Nya, et al. (2013)

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