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Cells
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TRAIL Receptors in Health and Diseases
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TRAIL Receptors in Health and Diseases

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

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 9345

Special Issue Editors

Prof. Dr. Paola Secchiero

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Guest Editor
Department of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Interests: translational research in oncology, onco-hematology, cardiovascular and metabolic diseases, eye diseases physiopathology and therapies; preclinical testing of innovative molecule/drugs and delivery systems
Special Issues, Collections and Topics in MDPI journals
Dr. Erika Rimondi

E-Mail Website
Guest Editor
1. Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
2. LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Interests: role of TRAIL and OPG systems in osteoclastic differentiation and cancer; apoptotic effects evaluation of different drugs in chronic lymphocytic leukemia models; circulating cytokines/chemokines assessment; morphological studies; transmission electron microscopy and immunohistochemistry
Special Issues, Collections and Topics in MDPI journals
Dr. Rebecca Voltan

E-Mail Website
Guest Editor
Department of Environmental and Prevention Sciences and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Interests: cancer; nanodelivery; MDM2 inhibitors; p53; TRAIL
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The tumor necrosis factor (TNF) superfamily member TRAIL (TNF-related apoptosis-inducing ligand) has been demonstrated to be involved in several physiological and pathological conditions, generating great interest as a potential disease biomarker and therapeutic target/strategy. The ability of TRAIL to induce apoptosis in cancer/transformed cells while preserving the normal ones in favor of alternative pathways has made TRAIL an appealing and interesting therapeutic target in cancer. However, we are dealing with a highly pleiotropic cytokine that plays key roles not only in cancer but also in other non-neoplastic diseases.

The complex mechanisms underlying the multifaceted biology of TRAIL still need to be fully clarified, but a key role is played by the composite ligand–receptor system of five cognate receptors that can be bound by TRAIL with different affinities under physiological conditions and in pathological contexts.

Overall, any effort made to gain insights into the biological mechanisms of the TRAIL receptor system and its role in physiological and pathological contexts will improve our understanding of the TRAIL ligand and its potential clinical applications.

This Special Issue of Cells focuses on novel aspects concerning cellular, molecular, and physiological traits of TRAIL biology via interaction with its receptors and how they affect human health and disease. We welcome original papers and review articles dealing with the latest advances coming from preclinical and clinical research.

Manuscripts can focus on healthy subjects/conditions and on different pathological settings including, but not limited to (cardio)vascular diseases, endocrinology, oncology, dermatology, immunology/inflammation, neurological diseases, pharmacology, diabetes, and aging.

Prof. Paola Secchiero
Dr. Erika Rimondi
Prof. Rebecca Voltan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • soluble and transmembrane TRAIL
  • TRAIL transmembrane death receptors and decoy receptors
  • osteoprotegerin
  • cellular, molecular, and physiological traits of TRAIL receptors
  • receptor activation and signal transduction
  • healthy status
  • disease development and progression
  • disease biomarkers
  • cardiovascular disease
  • cancer
  • neurological/neurodegenerative disease
  • diabetes

Published Papers (3 papers)

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Research

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14 pages, 1649 KiB  
Article
Selinexor Sensitizes TRAIL-R2-Positive TNBC Cells to the Activity of TRAIL-R2xCD3 Bispecific Antibody
by Silvia Martini, Mariangela Figini, Aurora Croce, Barbara Frigerio, Marzia Pennati, Alessandro Massimo Gianni, Cinzia De Marco, Maria Grazia Daidone, Christian Argueta, Yosef Landesman, Nadia Zaffaroni and Alessandro Satta
Cells 2020, 9(10), 2231; https://doi.org/10.3390/cells9102231 - 2 Oct 2020
Cited by 8 | Viewed by 3143
Abstract
Triple-negative breast cancer (TNBC) is an aggressive disease with poor prognosis and limited therapeutic options. Recent advances in the immunotherapy field have enabled the development of new treatment strategies, among which the use of bispecific antibodies (BsAbs), able to redirect T cells against [...] Read more.
Triple-negative breast cancer (TNBC) is an aggressive disease with poor prognosis and limited therapeutic options. Recent advances in the immunotherapy field have enabled the development of new treatment strategies, among which the use of bispecific antibodies (BsAbs), able to redirect T cells against tumors, has shown promising results. In particular, a BsAb that uses TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) as a target was constructed and demonstrated good results in redirecting CD3+ T cells to kill TRAIL-R2-expressing TNBC cells. In the present study, we investigated whether treatment with selinexor, a selective inhibitor of nuclear export (SINE) targeting exportin-1/chromosome maintenance protein 1 (XPO1/CRM1), could potentiate the antitumor activity of this BsAb. In combination experiments, we found that selinexor-exposed TNBC cells exhibited greater growth inhibition when treated with the TRAIL-R2xCD3 BsAb than that expected by simple additivity. Similarly, the apoptosis rate in selinexor/TRAIL-R2xCD3 BsAb-treated TNBC cells was significantly higher than that observed after exposure to either single agent. Together, our results suggest that the combination of selinexor and TRAIL-R2xCD3 BsAb can be a viable anticancer strategy and indicate this treatment as a promising therapeutic option for TNBC patients. Full article
(This article belongs to the Special Issue TRAIL Receptors in Health and Diseases)
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12 pages, 2007 KiB  
Article
Changes in the Concentration of Markers Participating in the Regulation of the Apoptosis Receptor Pathway Involving Soluble Tumour Necrosis Factor Ligand Inducing Apoptosis (sTRAIL) and Osteoprotegerin (OPG) in the Serum of Women with Ovarian Cancer—Participation in Pathogenesis or a Possible Clinical Use?
by Aleksandra Mielczarek-Palacz, Zdzisława Kondera-Anasz and Marta Smycz-Kubańska
Cells 2020, 9(3), 612; https://doi.org/10.3390/cells9030612 - 4 Mar 2020
Cited by 4 | Viewed by 2028
Abstract
Due to the ability to selectively induce apoptosis in cancer cells, the most interesting target for clinical research is the tumour necrosis factor ligand inducing apoptosis (TRAIL), which binds specific receptors, including osteoprotegerin (OPG). The aim of the study was to analyse the [...] Read more.
Due to the ability to selectively induce apoptosis in cancer cells, the most interesting target for clinical research is the tumour necrosis factor ligand inducing apoptosis (TRAIL), which binds specific receptors, including osteoprotegerin (OPG). The aim of the study was to analyse the concentration of soluble TRAIL (sTRAIL) and OPG in the serum of women with serous or mucinous ovarian cancer, taking into account different levels of cancer histological differentiation. The group included 97 women with the diagnosed Cystadenocarcinoma papillare serosum IIIc and Cystadenocarcinoma mucinosum IIIc. Concentrations of parameters were measured by ELISA. Analysis of the obtained results showed a statistically significantly higher concentration of sTRAIL and OPG in the serum of women with ovarian serous and mucinous cancer compared to the control group (p < 0.0001). Statistical significance was found between sTRAIL and OPG concentration in G1 and G3 serous cancer (p < 0.01) and in OPG mucinous cancer between G1 and G3 (p < 0.01) and G2 and G3 (p < 0.01). An important role in the pathogenesis of ovarian cancer is played by disorders of the apoptosis process involving the sTRAIL/OPG system, which are associated with the histological type and the degree of histological differentiation of the tumour. Determining the concentration of tested parameters in combination with other markers may be useful in the future in the diagnosis of ovarian cancer, but that requires further research. Full article
(This article belongs to the Special Issue TRAIL Receptors in Health and Diseases)
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Review

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12 pages, 2961 KiB  
Review
On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function
by Éva S. Vanamee and Denise L. Faustman
Cells 2020, 9(3), 764; https://doi.org/10.3390/cells9030764 - 20 Mar 2020
Cited by 22 | Viewed by 3795
Abstract
Tumor necrosis factor (TNF) superfamily ligands show diverse biological functions, such as the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer and autoimmunity. We review the latest literature on TNF receptor superfamily signaling with [...] Read more.
Tumor necrosis factor (TNF) superfamily ligands show diverse biological functions, such as the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer and autoimmunity. We review the latest literature on TNF receptor superfamily signaling with a focus on structure-function. Using combinatorics, we argue that receptors that cluster on the cell surface and are activated by membrane-bound ligands need to arrange in a highly ordered manner, as the probability of random ligand and receptor arrangements matching up for receptor activation is very low. A growing body of evidence indicates that antiparallel receptor dimers that sequester the ligand binding site cluster on the cell surface, forming a hexagonal lattice. Upon ligand binding, this arrangement puts the activated receptors at the right distance to accommodate the downstream signaling partners. The data also suggest that the same geometry is utilized regardless of receptor type. The unified model provides important clues about TNF receptor signaling and should aid the design of better therapies for cancer and various immune mediated diseases. Full article
(This article belongs to the Special Issue TRAIL Receptors in Health and Diseases)
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