Role of Microenvironment in the Control of Cell Proliferation, Death, and Autophagy

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

Deadline for manuscript submissions: 31 March 2024 | Viewed by 2510

Special Issue Editors

Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Hälsovägen 7C, Huddinge, 14157 Stockholm, Sweden
Interests: tumor microenvironment; stem cells; innate immunity; autophagy; cell death
Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Section of Human Anatomy, “Sapienza” University of Rome, Via A. Borelli 50, 00161 Rome, Italy
Interests: cell death; autophagy; cancer growth; organ homeostasis; tissue regeneration

Special Issue Information

Dear Colleagues,

In recent years, it has become clear that the tissue microenvironment consists in a dynamic population of cellular and non-cellular components influencing organ homeostasis in various ways. The microenvironment modulates cell activity, metabolism, differentiation, tissue development, and stem cell pool maintenance. Signals sent by nearby cells can have an impact on survival, proliferation, autophagy, and death. Such interactions control multiple intercellular and intracellular signaling pathways and affect extracellular matrix components, which can also lead to cancer growth and dissemination. Indeed, the tissue microenvironment can play a pivotal role in tumorigenesis and metastasis formation. In this Special Issue, we encourage the submission of manuscripts on novel mechanisms underlying the normal network of cellular and non-cellular components within healthy tissue microenvironments, as well as new discoveries on factors driving malignant transformations.

Dr. Luana Tomaipitinca
Dr. Claudia Giampietri
Guest Editors

Manuscript Submission Information

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Published Papers (2 papers)

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Research

17 pages, 4866 KiB  
Article
Cholangiocarcinoma Malignant Traits Are Promoted by Schwann Cells through TGFβ Signaling in a Model of Perineural Invasion
by Valerio de Franchis, Simonetta Petrungaro, Elisa Pizzichini, Serena Camerini, Marialuisa Casella, Francesca Somma, Enrico Mandolini, Guido Carpino, Diletta Overi, Vincenzo Cardinale, Antonio Facchiano, Antonio Filippini, Eugenio Gaudio, Cinzia Fabrizi and Claudia Giampietri
Cells 2024, 13(5), 366; https://doi.org/10.3390/cells13050366 - 20 Feb 2024
Viewed by 659
Abstract
The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that [...] Read more.
The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that in human intrahepatic CCA specimens with documented PNI, nerve-infiltrating CCA cells display positivity of the epithelial marker cytokeratin 7, lower with respect to the rest of the tumor mass. In an in vitro 3D model, CCA cells move towards a peripheral nerve explant allowing contact with Schwann cells (SCs) emerging from the nerve. Here, we show that SCs produce soluble factors that favor the migration, invasion, survival and proliferation of CCA cells in vitro. This effect is accompanied by a cadherin switch, suggestive of an epithelial–mesenchymal transition. The influence of SCs in promoting the ability of CCA cells to migrate and invade the extracellular matrix is hampered by a specific TGFβ receptor 1 (TGFBR1) antagonist. Differential proteomic data indicate that the exposure of CCA cells to SC secreted factors induces the upregulation of key oncogenes and the concomitant downregulation of some tumor suppressors. Taken together, these data concur in identifying SCs as possible promoters of a more aggressive CCA phenotype, ascribing a central role to TGFβ signaling in regulating this process. Full article
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18 pages, 7801 KiB  
Article
Effects of Simulated Microgravity In Vitro on Human Metaphase II Oocytes: An Electron Microscopy-Based Study
by Selenia Miglietta, Loredana Cristiano, Maria Salomé B. Espinola, Maria Grazia Masiello, Giulietta Micara, Ezio Battaglione, Antonella Linari, Maria Grazia Palmerini, Giuseppe Familiari, Cesare Aragona, Mariano Bizzarri, Guido Macchiarelli and Stefania A. Nottola
Cells 2023, 12(10), 1346; https://doi.org/10.3390/cells12101346 - 09 May 2023
Cited by 2 | Viewed by 1477
Abstract
The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts [...] Read more.
The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the high costs and lack of repeatability of the experiments. For these reasons, the use of microgravity simulators for studying, at the cellular level, the effects, such as those, obtained during/after a spatial trip, are developed to confirm that these models can be used in the study of body responses under conditions different from those found in a unitary Gravity environment (1 g). In view of this, this study aimed to investigate in vitro the effects of simulated microgravity on the ultrastructural features of human metaphase II oocytes using a Random Positioning Machine (RPM). We demonstrated for the first time, by Transmission Electron Microscopy analysis, that microgravity might compromise oocyte quality by affecting not only the localization of mitochondria and cortical granules due to a possible alteration of the cytoskeleton but also the function of mitochondria and endoplasmic reticulum since in RPM oocytes we observed a switch in the morphology of smooth endoplasmic reticulum (SER) and associated mitochondria from mitochondria-SER aggregates to mitochondria–vesicle complexes. We concluded that microgravity might negatively affect oocyte quality by interfering in vitro with the normal sequence of morphodynamic events essential for acquiring and maintaining a proper competence to fertilization in human oocytes. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: TGFβ released by Schwann cells increases cholangiocarcinoma malignant features inducing migration and proliferation in an in vitro model of perineural invasion.
Authors: Claudia Giampietri
Affiliation: “Sapienza” University of Rome
Abstract: Cholangiocarcinoma (CCa) is a highly neurotropic epithelial malignancy originating from bile duct. Patients with reported perineural invasion have a worse prognosis, though the biological reason for such worsening is yet unclear. Increasing evidence show activated Schwann cells (SC) involvement in the progression of cancers, like pancreatic ductal adenocarcinoma. By reproducing perineural invasion in vitro, we observed a neurotropism in HuCC-T1 CCa cell line, at least partly dependent by SC. We demonstrate here that SC conditioned medium is able to increase CCa malignant traits such as migration and proliferation, in two different cell lines, in a TGFβ dependent way.

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