Transcriptomic alterations in malignant pleural mesothelioma cells in response to long‑term treatment with bullfrog sialic acid‑binding lectin

Our plain-English summary of Transcriptomic alterations in malignant pleural mesothelioma cells in response to long‑term treatment with bullfrog sialic acid‑binding lectin, by T. Tatsuta, A. Nakasato, S. Sugawara, et al (Molecular Medicine Reports, 2021).

The study

• Authors: T. Tatsuta, A. Nakasato, S. Sugawara, M. Hosono
• Journal: Molecular Medicine Reports
• Published: 2021;23(6)
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a universally lethal type of cancer that is increasing in incidence worldwide; therefore, the development of new drugs for MPM is an urgent task. Bullfrog sialic acid‑binding lectin (cSBL) is a multifunctional protein that has carbohydrate‑binding and ribonuclease activities. cSBL exerts marked antitumor activity against numerous types of cancer cells, with low toxicity to normal cells. Although in vitro and in vivo studies revealed that cSBL was effective against MPM, the mechanism by which cSBL exerts antitumor effects is not fully understood. To further understand the mechanism of action of cSBL, the present study aimed to identify the key molecules whose expression was affected by cSBL. The present study established cSBL‑resistant MPM cells. Microarray analyses revealed that there were significant pleiotropic changes in the expression profiles of several genes, including multiple genes involved in metabolic pathways in cSBL‑resistant cells. Furthermore, the expression of some members of the aldo‑keto reductase family was revealed to be markedly downregulated in these cells. Among these, it was particularly interesting that cSBL action reduced the level of AKR1B10, which has been reported as a biomarker candidate for MPM prognosis. These findings revealed novel aspects of the effect of cSBL, which may contribute to the development of new therapeutic strategies for MPM.

In plain English

This was a laboratory study of human malignant pleural mesothelioma cells grown in dishes. It did not study asbestos exposure or patients. The authors grew the H28 mesothelioma cell line in slowly rising amounts of bullfrog sialic acid-binding lectin (cSBL), an experimental anticancer protein, until they obtained five clones resistant to it. Two clones (cSR-A1 and cSR-B1) were studied further. In a 12-day colony test their resistance rates, compared with the original cells, were 15.3 and 14.5. In a 72-hour viability test the rates were only 4.4 and 4.6. Gene activity was measured with a microarray, a test that checks thousands of genes at once. It showed 927 genes changed in both resistant clones, including many tied to metabolism. Several aldo-keto reductase (AKR) genes were strongly reduced, and lower AKR1B10 protein was confirmed in both clones. The authors noted that some changed genes may relate to resistance itself rather than to direct effects of cSBL. They concluded that long-term cSBL treatment affected the cells by dysregulating multiple genes, and that the reduction of AKR1B10 may offer new possibilities for cancer therapy.

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-line experiment: drug-resistant cells were created and their gene expression compared with the original cells by microarray, RT-qPCR and western blotting
• Who was studied: The human malignant pleural mesothelioma cell line H28 and five cSBL-resistant clones derived from it (cSR-A1, -A2, -B1, -B2, -C1). Clones cSR-A1 and cSR-B1 were used for most analyses. No patients were studied.
• Exposure: Long-term culture with bullfrog sialic acid-binding lectin (cSBL), increased stepwise from 0.01 µM to 0.5 µM over about 50 passages. Onconase (ONC) and doxorubicin (DOX) were also tested for comparison. Asbestos was not an exposure in this study.
• Main results:
  • In the colony formation assay, the resistance rates for cSR-A1 and cSR-B1 compared with parental H28 cells were 15.3 and 14.5
  • In the 72-hour WST-8 viability assay, the resistance rates to cSBL were 4.4 (cSR-A1) and 4.6 (cSR-B1)
  • Resistance rates to onconase were 1.6 (cSR-A1) and 2.0 (cSR-B1); to doxorubicin they were 0.7 and 1.0
  • Growth rates did not differ significantly among H28, cSR-A1 and cSR-B1 cells
  • After cSBL treatment, cSR-B1 cells had less cleaved caspase-3 (a marker of cell death) than H28 cells, but the difference was not significant
  • 927 genes (440 up, 487 down) were changed in both resistant clones compared with H28 cells, out of 37,756 coding transcripts (2.46%)
  • In pathway analysis of the changed genes, metabolism of xenobiotics by cytochrome P450 was the most significant pathway
  • In the microarray, six AKR family genes were decreased 9.1- to 562.0-fold in the resistant cells
  • RT-qPCR confirmed reduced expression of THY1, AKR1B15, AKR1B10, SLC47A2 and CBR1 in both resistant clones, decreased 22.8- to 483.2-fold
  • AKR1B10 protein was significantly decreased in cSR-A1 and cSR-B1 cells compared with H28 cells
  • Expression of the transporter genes ABCC2 and ABCA1 was lower in the resistant cells (17.3 and 4.7 times lower)
• The authors' conclusion: The authors concluded that long-term cSBL treatment affected malignant mesothelioma cells by dysregulating multiple genes. They also concluded that, because cSBL significantly reduced AKR family members, especially AKR1B10, it may offer new possibilities for cancer therapy.
• Limitations the authors state:
  • Because resistant cells were used, the changed genes may include genes involved in resistance to cSBL
  • The changed genes may include genes not directly affected by cSBL

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, Biomarker, Prognosis.

Related studies

• Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma — T. Satoh, T. Tatsuta, et al. (2017)
• Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo — T. Tatsuta, T. Satoh, et al. (2018)
• Sialic acid-binding lectin (leczyme) induces apoptosis to malignant mesothelioma and exerts synergistic antitumor effects with TRAIL — T. Tatsuta, M. Hosono, et al. (2014)
• Sialic acid mediates the initial binding of positively charged inorganic particles to alveolar macrophage membranes — J.E. Gallagher, G. George, et al. (1987)
• Lectin binding properties of cells from serous effusion and peritoneal washing specimens — P.W. Shield (1989)
• Insights Into Genomic Drivers, Transcriptomic Heterogeneity, and Therapeutic Vulnerabilities From Novel Mesothelioma Cell Lines — Y. Wu, F. Cao, et al. (2026)

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