Frontiers in Cell and Developmental Biology

Our medical research library holds 8 studies published in Frontiers in Cell and Developmental Biology (2019–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 8 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Frontiers Media S.A
• Published: 2013 to the present, Switzerland
• Language: English
• ISSN: 2296-634X (electronic)
• Its record in the NLM Catalog

2020s

• FGF2 promotes the expansion of parietal mesothelial progenitor pools and inhibits BMP4-mediated smooth muscle cell differentiation. Y. Hwang, Y. Shimamura, J. Tanaka, et al. 2024;12:1387237. PubMed · Publisher · Free full text

  Abstract

  Mesothelial cells, in the outermost layer of internal organs, are essential for both organ development and homeostasis. Although the parietal mesothelial cell is the primary origin of mesothelioma that may highjack developmental signaling, the signaling pathways that orchestrate developing parietal mesothelial progenitor cell (MPC) behaviors, such as MPC pool expansion, maturation, and differentiation, are poorly understood. To address it, we established a robust protocol for culturing WT1+ MPCs isolated from developing pig and mouse parietal thorax. Quantitative qPCR and immunostaining analyses revealed that BMP4 facilitated MPC differentiation into smooth muscle cells (SMCs). In contrast, FGF2 significantly promoted MPC progenitor pool expansion but blocked the SMC differentiation. BMP4 and FGF2 counterbalanced these effects, but FGF2 had the dominant impact in the long-term culture. A Wnt activator, CHIR99021, was pivotal in MPC maturation to CALB2+ mesothelial cells, while BMP4 or FGF2 was limited. Our results demonstrated central pathways critical for mesothelial cell behaviors.

  Copyright © 2024 Hwang, Shimamura, Tanaka, Miura, Sawada, Sarmah, Shimizu, Kondo, Lee, Martini, Ninish, Yan, Yamada and Mori.

• New insight into the CNC-bZIP member, NFE2L3, in human diseases. G. Xiong, J. Li, F. Yao, et al. 2024;12:1430486. Review PubMed · Publisher · Free full text

  Abstract

  Nuclear factor erythroid 2 (NF-E2)-related factor 3 (NFE2L3), a member of the CNC-bZIP subfamily and widely found in a variety of tissues, is an endoplasmic reticulum (ER) membrane-anchored transcription factor that can be released from the ER and moved into the nucleus to bind the promoter region to regulate a series of target genes involved in antioxidant, inflammatory responses, and cell cycle regulation in response to extracellular or intracellular stress. Recent research, particularly in the past 5 years, has shed light on NFE2L3's participation in diverse biological processes, including cell differentiation, inflammatory responses, lipid homeostasis, immune responses, and tumor growth. Notably, NFE2L3 has been identified as a key player in the development and prognosis of multiple cancers including colorectal cancer, thyroid cancer, breast cancer, hepatocellular carcinoma, gastric cancer, renal cancer, bladder cancer, esophageal squamous cell carcinoma, T cell lymphoblastic lymphoma, pancreatic cancer, and squamous cell carcinoma. Furthermore, research has linked NFE2L3 to other cancers such as lung adenocarcinoma, malignant pleural mesothelioma, ovarian cancer, glioblastoma multiforme, and laryngeal carcinoma, indicating its potential as a target for innovative cancer treatment approaches. Therefore, to gain a better understanding of the role of NFE2L3 in disease, this review offers insights into the discovery, structure, function, and recent advancements in the study of NFE2L3 to lay the groundwork for the development of NFE2L3-targeted cancer therapies.

  Copyright © 2024 Xiong, Li, Yao, Yang and Xiang.

• Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma. S. Zhang, S. Li, Y. Wei, et al. 2022;10:879278. PubMed · Publisher · Free full text

  Abstract

  Messenger RNA vaccines are considered to be a promising strategy in cancer immunotherapy, while their application on mesothelioma is still largely uncharacterized. This study aimed to identify potential antigens in mesothelioma for anti-mesothelioma mRNA vaccine development, and further determine the immune subtypes of mesothelioma for selection of suitable candidates from an extremely heterogeneous population. Gene expression data and corresponding clinicopathological information were obtained from the TCGA and gene expression omnibus, respectively. Then, the genetic alterations were compared and visualized using cBioPortal, and differentially expressed genes and their prognostic signatures were identified by GEPIA. The relationship between tumor-infiltrating immune cells and the expression of tumor antigens was systematically evaluated by TIMER online. Finally, the immune subtypes and immune landscape of mesothelioma were separately analyzed using consensus cluster and graph learning-based dimensional reduction. A total of five potential tumor antigens correlated with prognosis and infiltration of antigen-presenting cells, including AUNIP, FANCI, LASP1, PSMD8, and XPO5 were identified. Based on the expression of immune-related genes, patients with mesothelioma were divided into two immune subtypes (IS1 and IS2). Each subtype exhibited differential molecular, cellular and clinical properties. Patients with the IS1 subtype were characterized by an immune "cold" phenotype, displaying superior survival outcomes, whereas those with the IS2 subtype were characterized by an immune "hot" and immunosuppressive phenotype. Furthermore, immune checkpoints and immunogenic cell death modulators were differentially expressed between the IS1 and IS2 immune subtype tumors. The immunogenomic landscape of mesothelioma revealed a complex tumor immune microenvironment between individual patients. AUNIP, FANCI, LASP1, PSMD8, and XPO5 are putative antigens for the development of anti-mesothelioma mRNA vaccine and patients with the IS1 subtype may be considered for vaccination.

  Copyright © 2022 Zhang, Li, Wei, Xiong, Liu, Hu, Zeng, Tang and Ouyang.

• Nintedanib and Dasatinib Treatments Induce Protective Autophagy as a Potential Resistance Mechanism in MPM Cells. L. Hegedüs, K.D. Szücs, M. Kudla, et al. 2022;10:852812. PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM) is a rare type of cancer with a grim prognosis. So far, no targetable oncogenic mutation was identified in MPM and biomarkers with predictive value toward drug sensitivity or resistance are also lacking. Nintedanib (BIBF1120) is a small-molecule tyrosine kinase inhibitor that showed promising efficacy preclinically and in phase II trial in MPM as an angiogenesis inhibitor combined with chemotherapy. However, the extended phase III trial failed. In this study, we investigated the effect of nintedanib on one of its targets, the SRC kinase, in two commercial and six novel MPM cell lines. Surprisingly, nintedanib treatment did not inhibit SRC activation in MPM cells and even increased phosphorylation of SRC in several cell lines. Combination treatment with the SRC inhibitor dasatinib could reverse this effect in all cell lines, however, the cellular response was dependent on the drug sensitivity of the cells. In 2 cell lines, with high sensitivity to both nintedanib and dasatinib, the drug combination had no synergistic effect but cell death was initiated. In 2 cell lines insensitive to nintedanib combination treatment reduced cell viability synergisticaly without cell death. In contrast, in these cells both treatments increased the autophagic flux assessed by degradation of the autophagy substrate p62 and increased presence of LC3B-II, increased number of GFP-LC3 puncta and decreased readings of the HiBiT-LC3 reporter. Additionaly, autophagy was synergistically promoted by the combined treatment. At the transcriptional level, analysis of lysosomal biogenesis regulator Transcription Factor EB (TFEB) showed that in all cell lines treated with nintedanib and to a lesser extent, with dasatinib, it became dephosphorylated and accumulated in the nucleus. Interestingly, the expression of certain known TFEB target genes implicated in autophagy or lysosomal biogenesis were significantly modified only in 1 cell line. Finally, we showed that autophagy induction in our MPM cell lines panel by nintedanib and dasatinib is independent of the AKT/mTOR and the ERK pathways. Our study reveals that autophagy can serve as a cytoprotective mechanism following nintedanib or dasatinib treatments in MPM cells.

  Copyright © 2022 Hegedüs, Szücs, Kudla, Heidenreich, Jendrossek, Peña-Llopis, Garay, Czirok, Aigner, Plönes, Vega-Rubin-de-Celis and Hegedüs.

• Possible Therapeutic Utility of anti-Cell Adhesion Molecule 1 Antibodies for Malignant Pleural Mesothelioma. M. Hagiyama, T. Mimae, A. Wada, et al. 2022;10:945007. PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor, and the effective therapeutic drugs are limited. Thus, the establishment of novel therapeutic method is desired. Considerable proportion of MPMs are shown to express cell adhesion molecule 1 (CADM1), and to use CADM1 to bind to and proliferate on the pleural mesothelial surface, suggesting that CADM1 is a possible therapeutic target. Here, anti-CADM1 ectodomain chicken monoclonal antibodies, 3E1 and 9D2, were examined for their possible therapeutic utility. The full-length form of CADM1 was expressed in eight out of twelve human MPM cell lines. MPM cell lines were cultured on a confluent monolayer of mesothelial MeT-5A cells in the presence of 9D2, the neutralizing antibody. 9D2 suppressed the cell growth of CADM1-positive MPM cells with the loss and aggregation of CADM1 molecules on the MPM cell membrane, but not of CADM1-negative MPM cells. Co-addition of 3E1, lacking the neutralizing action, enhanced the growth-suppressive effect of 9D2. The two antibodies were tested as drug delivery vectors. 3E1 was converted into a humanized antibody (h3E1) and conjugated with monomethyl auristatin E (MMAE), a tubulin polymerization inhibitor. When the resulting h3E1-MMAE antibody-drug conjugate (ADC) was added to the standard cultures of CADM1-positive MPM cells, it suppressed the cell growth in a dose-dependent manner. Co-addition of 9D2 enhanced the growth-suppressive effect of h3E1-MMAE ADC. Anti-CADM1 ectodomain antibodies were suggested to serve as both antibody drugs and drug vectors in the treatment of MPM.

  Copyright © 2022 Hagiyama, Mimae, Wada, Takeuchi, Yoneshige, Inoue, Kotoku, Hamada, Sekido, Okada and Ito.

• Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells. M. Rossini, F. Martini, E. Torreggiani, et al. 2020;8:534499. PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.

  Copyright © 2021 Rossini, Martini, Torreggiani, Fortini, Aquila, Vieceli Dalla Sega, Patergnani, Pinton, Maniscalco, Cavallesco, Rizzo and Tognon.

2010s

• Corrigendum: Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma. T.G. Johnson, K. Schelch, S. Mehta, et al. 2019;7:293. PubMed · Publisher · Free full text

  Abstract

  [This corrects the article doi:10.3389/fcell.2019.00221.].

  Copyright © 2019 Johnson, Schelch, Mehta, Burgess and Reid.

• Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma. T.G. Johnson, K. Schelch, S. Mehta, et al. 2019;7:221. Review PubMed · Publisher · Free full text

  Abstract

  Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.

  Copyright © 2019 Johnson, Schelch, Mehta, Burgess and Reid.

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