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Mesothelial Cell: Its Repair, Plasticity, and Relationship with Tumor Dissemination
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Mesothelial Cell: Its Repair, Plasticity, and Relationship with Tumor Dissemination

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 8010

Special Issue Editors

Prof. Dr. Akira Hara

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Guest Editor
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Interests: pathology; neuropathology; stem cell; immunohistochemistry; regenerative medicine; cancer; oncogene
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Hiroyuki Tomita

E-Mail
Guest Editor
Department of Tumor Pathology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
Interests: pathology; tumor microenvironment; carcinogenesis; stem cell; mouse models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesothelial cells form a specialized pavement-like single layer of cells that covers the body’s serous cavities and internal organs. The primary function of this layer, called the mesothelium, is to provide a slippery, non-adhesive protective surface. Furthermore, mesothelial cells also play other important roles, such as fluid and cell transport, antigen presentation, inflammation and tissue repair, coagulation and fibrinolysis, and cancer cell adhesion. When the mesothelium is injured, mesothelial cells migrate from the edge of the lesion toward the center of the wound, where the cells drop into the serous fluid and adhere to and are incorporated into the regenerating mesothelium. When healing is inhibited, fibrous serous adhesions form between the organ and the body wall, suppressing pivotal thoracic and abdominal motility. Mesothelial cells are also thought to be involved in both the spread of cancer dissemination within the serous cavity and the inhibition of its growth. On the other hand, tumorigenesis of mesothelial cells leads to malignant mesothelioma, a malignant tumor that occurs primarily in the pleura. In this Special Issue, we aim to cover all topics related to mesothelial cells, from basic molecular research to clinical applications.

Prof. Dr. Akira Hara
Prof. Dr. Hiroyuki Tomita
Guest Editors

Manuscript Submission Information

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Keywords

  • mesothelial cell
  • mesothelium
  • inflammation
  • tissue repair
  • cancer
  • cancer dissemination
  • tumorigenesis
  • mesothelioma

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Published Papers (3 papers)

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Research

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15 pages, 4378 KiB  
Article
Toll-like Receptor 2 Mediates VEGF Overexpression and Mesothelial Hyperpermeability in Tuberculous Pleural Effusion
by Wei-Lin Chen, Kai-Ling Lee, Kevin S. Lai, Jie-Heng Tsai, Shih-Hsin Hsiao and Chi-Li Chung
Int. J. Mol. Sci. 2023, 24(3), 2846; https://doi.org/10.3390/ijms24032846 - 2 Feb 2023
Cited by 4 | Viewed by 1723
Abstract
Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth [...] Read more.
Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2/VEGF pathway may confer a potential treatment strategy for TBPE. Full article
(This article belongs to the Special Issue Mesothelial Cell: Its Repair, Plasticity, and Relationship with Tumor Dissemination)
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Review

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13 pages, 625 KiB  
Review
Regulation of Mesothelial Cell Fate during Development and Human Diseases
by Toshiaki Taniguchi, Hiroyuki Tomita, Tomohiro Kanayama, Kazumasa Mogi, Yoshihiro Koya, Yoshihiko Yamakita, Masato Yoshihara, Hiroaki Kajiyama and Akira Hara
Int. J. Mol. Sci. 2022, 23(19), 11960; https://doi.org/10.3390/ijms231911960 - 8 Oct 2022
Cited by 3 | Viewed by 2740
Abstract
Mesothelial cells (MCs) play a classic role in maintaining homeostasis in pleural, peritoneal, and pericardial cavities. MCs work as lubricants to reduce friction between organs, as regulators of fluid transport, and as regulators of defense mechanisms in inflammation. MCs can differentiate into various [...] Read more.
Mesothelial cells (MCs) play a classic role in maintaining homeostasis in pleural, peritoneal, and pericardial cavities. MCs work as lubricants to reduce friction between organs, as regulators of fluid transport, and as regulators of defense mechanisms in inflammation. MCs can differentiate into various cells, exhibiting epithelial and mesenchymal characteristics. MCs have a high potential for differentiation during the embryonic period when tissue development is active, and this potential decreases through adulthood. The expression of the Wilms’ tumor suppressor gene (Wt1), one of the MC markers, decreased uniformly and significantly from the embryonic period to adulthood, suggesting that it plays a major role in the differentiation potential of MCs. Wt1 deletion from the embryonic period results in embryonic lethality in mice, and even Wt1 knockout in adulthood leads to death with rapid organ atrophy. These findings suggest that MCs expressing Wt1 have high differentiation potential and contribute to the formation and maintenance of various tissues from the embryonic period to adulthood. Because of these properties, MCs dynamically transform their characteristics in the tumor microenvironment as cancer-associated MCs. This review focuses on the relationship between the differentiation potential of MCs and Wt1, including recent reports using lineage tracing using the Cre-loxP system. Full article
(This article belongs to the Special Issue Mesothelial Cell: Its Repair, Plasticity, and Relationship with Tumor Dissemination)
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Other

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8 pages, 40032 KiB  
Case Report
Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation
by Gabriella Serio, Federica Pezzuto, Francesco Fortarezza, Andrea Marzullo, Maria Celeste Delfino, Antonio d’Amati, Daniele Egidio Romano, Sonia Maniglio, Concetta Caporusso, Teresa Lettini, Domenica Cavone and Luigi Vimercati
Int. J. Mol. Sci. 2022, 23(5), 2630; https://doi.org/10.3390/ijms23052630 - 27 Feb 2022
Cited by 4 | Viewed by 2710
Abstract
There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos [...] Read more.
There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ. Full article
(This article belongs to the Special Issue Mesothelial Cell: Its Repair, Plasticity, and Relationship with Tumor Dissemination)
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