Cell Methods: Molecular Events in the Progression of Human Tumor Cell Lines

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: closed (25 September 2023) | Viewed by 8429

Special Issue Editor


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Guest Editor
1. Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, 03203 Alicante, Spain
2. Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, Spain
Interests: biological systems; neuroscience; cancer; new therapies; drug delivery systems

Special Issue Information

Dear Colleagues,

Multiple events lead to the beginning and development of cancer, and the understanding of the fundamentals of how cancer cells form and proliferate has become crucial to cancer treatment and prevention. It is important to know how tumors form, why they persist, and the reasons underlying their spread through the body since those steps will have an impact on the prognosis of cancer patients. The uncontrolled growth exhibited by cancer cells results in accumulated abnormalities in multiple cell regulatory systems and is reflected in several aspects of cell behavior that distinguish cancer cells from their normal counterparts. The development of new tools, together with genomic and computational technologies, has helped to increase our knowledge regarding these cellular changes that drive cancer. Now, we have the capacity to characterize and compare thousands of patient tumors to identify factors that influence cancer behavior. However, it has recently become clear that only a small fraction of tumor cells within a single tumor may have the capacity to divide and sustain tumor growth. Therefore, studying human cancer on a cell-by-cell basis is critical to understand the clinical consequences. In this issue, we address the approaches followed by tumor cells at the different stages of tumor initiation, progression, and metastasis and the clinical relevance. 

Dr. Camino de Juan Romero
Guest Editor

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Keywords

  • cancer
  • cell death
  • new strategies
  • proliferation
  • cancer treatment

Published Papers (4 papers)

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Research

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15 pages, 1618 KiB  
Article
Defining a Correlative Transcriptional Signature Associated with Bulk Histone H3 Acetylation Levels in Adult Glioblastomas
by Irati Hervás-Corpión, Jorge Navarro-Calvo, Paula Martín-Climent, Marianela Iriarte-Gahete, Noelia Geribaldi-Doldán, Carmen Castro and Luis M. Valor
Cells 2023, 12(3), 374; https://doi.org/10.3390/cells12030374 - 19 Jan 2023
Cited by 2 | Viewed by 1917
Abstract
Glioblastoma (GB) is the most prevalent primary brain cancer and the most aggressive form of glioma because of its poor prognosis and high recurrence. To confirm the importance of epigenetics in glioma, we explored The Cancer Gene Atlas (TCGA) database and we found [...] Read more.
Glioblastoma (GB) is the most prevalent primary brain cancer and the most aggressive form of glioma because of its poor prognosis and high recurrence. To confirm the importance of epigenetics in glioma, we explored The Cancer Gene Atlas (TCGA) database and we found that several histone/DNA modifications and chromatin remodeling factors were affected at transcriptional and genetic levels in GB compared to lower-grade gliomas. We associated these alterations in our own cohort of study with a significant reduction in the bulk levels of acetylated lysines 9 and 14 of histone H3 in high-grade compared to low-grade tumors. Within GB, we performed an RNA-seq analysis between samples exhibiting the lowest and highest levels of acetylated H3 in the cohort; these results are in general concordance with the transcriptional changes obtained after histone deacetylase (HDAC) inhibition of GB-derived cultures that affected relevant genes in glioma biology and treatment (e.g., A2ML1, CD83, SLC17A7, TNFSF18). Overall, we identified a transcriptional signature linked to histone acetylation that was potentially associated with good prognosis, i.e., high overall survival and low rate of somatic mutations in epigenetically related genes in GB. Our study identifies lysine acetylation as a key defective histone modification in adult high-grade glioma, and offers novel insights regarding the use of HDAC inhibitors in therapy. Full article
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15 pages, 1656 KiB  
Article
Exploring Dynamic Metabolome of the HepG2 Cell Line: Rise and Fall
by Olga I. Kiseleva, Ilya Yu. Kurbatov, Viktoriia A. Arzumanian, Ekaterina V. Ilgisonis, Igor V. Vakhrushev, Alexey Yu. Lupatov, Elena A. Ponomarenko and Ekaterina V. Poverennaya
Cells 2022, 11(22), 3548; https://doi.org/10.3390/cells11223548 - 10 Nov 2022
Cited by 5 | Viewed by 1827
Abstract
Both biological and technical variations can discredit the reliability of obtained data in omics studies. In this technical note, we investigated the effect of prolonged cultivation of the HepG2 hepatoma cell line on its metabolomic profile. Using the GC × GC-MS approach, we [...] Read more.
Both biological and technical variations can discredit the reliability of obtained data in omics studies. In this technical note, we investigated the effect of prolonged cultivation of the HepG2 hepatoma cell line on its metabolomic profile. Using the GC × GC-MS approach, we determined the degree of metabolic variability across HepG2 cells cultured in uniform conditions for 0, 5, 10, 15, and 20 days. Post-processing of obtained data revealed substantial changes in relative abundances of 110 metabolites among HepG2 samples under investigation. Our findings have implications for interpreting metabolomic results obtained from immortal cells, especially in longitudinal studies. There are still plenty of unanswered questions regarding metabolomics variability and many potential areas for future targeted and panoramic research. However, we suggest that the metabolome of cell lines is unstable and may undergo significant transformation over time, even if the culture conditions remain the same. Considering metabolomics variability on a relatively long-term basis, careful experimentation with particular attention to control samples is required to ensure reproducibility and relevance of the research results when testing both fundamentally and practically significant hypotheses. Full article
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28 pages, 2565 KiB  
Article
Human Enzyme PADI4 Binds to the Nuclear Carrier Importin α3
by José L. Neira, Bruno Rizzuti, Olga Abián, Salomé Araujo-Abad, Adrián Velázquez-Campoy and Camino de Juan Romero
Cells 2022, 11(14), 2166; https://doi.org/10.3390/cells11142166 - 11 Jul 2022
Cited by 7 | Viewed by 2025
Abstract
PADI4 is a peptidyl-arginine deiminase (PADI) involved in the conversion of arginine to citrulline. PADI4 is present in macrophages, monocytes, granulocytes, and several cancer cells. It is the only PADI family member observed within both the nucleus and the cytoplasm. PADI4 has a [...] Read more.
PADI4 is a peptidyl-arginine deiminase (PADI) involved in the conversion of arginine to citrulline. PADI4 is present in macrophages, monocytes, granulocytes, and several cancer cells. It is the only PADI family member observed within both the nucleus and the cytoplasm. PADI4 has a predicted nuclear localization sequence (NLS) comprising residues Pro56 to Ser83, to allow for nuclear translocation. Recent predictors also suggest that the region Arg495 to Ile526 is a possible NLS. To understand how PADI4 is involved in cancer, we studied the ability of intact PADI4 to bind importin α3 (Impα3), a nuclear transport factor that plays tumor-promoting roles in several cancers, and its truncated species (ΔImpα3) without the importin-binding domain (IBB), by using fluorescence, circular dichroism (CD), and isothermal titration calorimetry (ITC). Furthermore, the binding of two peptides, encompassing the first and the second NLS regions, was also studied using the same methods and molecular docking simulations. PADI4 interacted with both importin species, with affinity constants of ~1–5 µM. The isolated peptides also interacted with both importins. The molecular simulations predict that the anchoring of both peptides takes place in the major binding site of Impα3 for the NLS of cargo proteins. These findings suggest that both NLS regions were essentially responsible for the binding of PADI4 to the two importin species. Our data are discussed within the framework of a cell mechanism of nuclear transport that is crucial in cancer. Full article
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Review

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17 pages, 1038 KiB  
Review
Pericyte–Glioblastoma Cell Interaction: A Key Target to Prevent Glioblastoma Progression
by Ana Pombero, Raquel Garcia-Lopez and Salvador Martínez
Cells 2023, 12(9), 1324; https://doi.org/10.3390/cells12091324 - 05 May 2023
Cited by 3 | Viewed by 2093
Abstract
Multiple biological processes rely on direct intercellular interactions to regulate cell proliferation and migration in embryonic development and cancer processes. Tumor development and growth depends on close interactions between cancer cells and cells in the tumor microenvironment. During embryonic development, morphogenetic signals and [...] Read more.
Multiple biological processes rely on direct intercellular interactions to regulate cell proliferation and migration in embryonic development and cancer processes. Tumor development and growth depends on close interactions between cancer cells and cells in the tumor microenvironment. During embryonic development, morphogenetic signals and direct cell contacts control cell proliferation, polarity, and morphogenesis. Cancer cells communicate with cells in the tumor niche through molecular signals and intercellular contacts, thereby modifying the vascular architecture and antitumor surveillance processes and consequently enabling tumor growth and survival. While looking for cell-to-cell signaling mechanisms that are common to both brain development and cancer progression, we have studied the infiltration process in glioblastoma multiforme (GBM), which is the most malignant primary brain tumor and with the worst prognosis. Cell-to-cell contacts, by means of filopodia-like structures, between GBM cells and brain pericytes (PCs) are necessary for adequate cell signaling during cancer infiltration; similarly, contacts between embryonic regions, via cytonemes, are required for embryo regionalization and development. This GBM–PC interaction provokes two important changes in the physiological function of these perivascular cells, namely, (i) vascular co-option with changes in cell contractility and vascular malformation, and (ii) changes in the PC transcriptome, modifying the microvesicles and protein secretome, which leads to the development of an immunosuppressive phenotype that promotes tumor immune tolerance. Moreover, the GTPase Cdc42 regulates cell polarity across organisms, from yeast to humans, playing a central role in GBM cell–PC interaction and maintaining vascular co-option. As such, a review of the molecular and cellular mechanisms underlying the development and maintenance of the physical interactions between cancer cells and PCs is of particular interest. Full article
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