Targeting Calcium Signalling in Malignant Mesothelioma

Our plain-English summary of Targeting Calcium Signalling in Malignant Mesothelioma, by S. Martinotti, M. Patrone, F. Moccia, et al (Cancers, 2019).

The study

• Authors: S. Martinotti, M. Patrone, F. Moccia, E. Ranzato
• Journal: Cancers
• Published: 2019;11(12)
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Calcium ions (Ca2+) are central in cancer development and growth, serving as a major signaling system determining the cell's fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca2+ permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca2+toolkit in this disease. Moreover, the established sensitivity of some Ca2+channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy.

In plain English

This article is a review, not a new study. The authors summarized earlier research on calcium signalling in malignant mesothelioma. Calcium signals are changes in calcium levels inside cells that switch on other cell processes; a network of channels, pumps and transporters, called the calcium-signalling toolkit, controls those levels. The authors described mesothelioma as normally linked to prior asbestos exposure, and noted that few data were available on calcium in this cancer. The review covered reports on a potassium channel, KCa1.1, found at higher levels in mesothelioma cells than in a normal mesothelial cell line. It covered T-type calcium channels, which the authors' own earlier study had found more present in mesothelioma patient tissues than in normal mesothelial tissue. It also covered the protein calretinin, the BAP1 gene, and reports that asbestos can trigger a cell stress response altering calcium release. The review reported no new patient or laboratory data. The authors concluded that changes in calcium channels seem to be a distinguishing sign of mesothelioma cells, that some are attractive treatment targets, and that additional studies are essential.

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: Narrative review of published research on calcium signalling in malignant mesothelioma
• Who was studied: No study population of its own. The review covered published laboratory and tissue studies of mesothelioma cells and calcium-handling molecules, which the authors said were few.
• Exposure: No exposure was measured. The review described mesothelioma as normally linked to prior asbestos exposure (job-related or, less often, domestic or environmental). It summarized other authors' suggestion that asbestos can induce a stress response that alters calcium release in cells. No specific fiber type is discussed in the article's own text.
• Main results:
  • The review explained that calcium signals are small changes in calcium levels inside cells that activate other cell processes. It said these levels are regulated by a network of channels and transporters, called the calcium-signalling toolkit.
  • The review reported that Cheng et al. found the potassium channel KCa1.1 expressed at higher levels in mesothelioma cells than in a normal mesothelial cell line (MeT-5A).
  • The authors described their own earlier study (Ranzato et al. 2012), which found T-type calcium channels more present in mesothelioma patient tissues than in normal mesothelial tissue.
  • The review cited earlier work suggesting that the calcium-binding protein calretinin may have a role in how mesothelioma begins.
  • The review cited earlier work reporting somatic BAP1 point mutations in up to 60% of sporadic mesothelioma.
  • The review reported that Kamp et al. found asbestos induced a stress response that caused calcium release in alveolar epithelial cells (lung cells).
  • The review reported that Patergnani and colleagues found a reduced level of the mitochondrial calcium uniporter (MCU) in mesothelioma cells compared with normal mesothelial cells. That team linked this to the unresponsiveness of mesothelioma cells to signals that normally trigger cell death.
• The authors' conclusion: The authors concluded that changes in the expression and/or activity of calcium-permeable ion channels seem to be a distinguishing sign of mesothelioma cells. They said that the sensitivity of some of these channels to selective drugs makes them attractive targets for mesothelioma management.
• Limitations the authors state:
  • The authors stated that few data are available on the role of calcium in mesothelioma.
  • The authors stated that the low sensitivity of drugs acting on calcium handling is one of the main limits for clinical use.
  • The authors stated that additional studies are needed to work out the best treatment strategy and the role of calcium signalling in this disease.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Prognosis, Serosal Surface, Asbestos Exposure, Overall Survival, Chemotherapy, Mesothelioma.

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