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Cancers
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Targeting Human Glioblastoma Stem-Like Cells (GSCs)
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Targeting Human Glioblastoma Stem-Like Cells (GSCs)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 3745

Special Issue Editors

Dr. Benedikt Linder

E-Mail Website
Guest Editor
Experimental Neurosurgery, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
Interests: brain tumors; cancer; cancer stem cells; ex vivo models; developmental signaling pathways in cancer; vitamin D3; migration and infiltration of cancer cells
Special Issues, Collections and Topics in MDPI journals
Dr. Ander Matheu

E-Mail Website
Guest Editor
Cellular Oncology Group, Biodonostia Health Research Institute, E-20014 San Sebastian, Spain
Interests: stem cell biology; oncology; aging; frailty; neuroscience
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma remains a virtually incurable disease with a dismal prognosis for patients and a plethora of open questions. The current standard therapy consists of surgery, radiochemotherapy and, in some cases, the application of tumor-treating fields. Even though promising new therapeutic avenues are underway, novel and especially directed approaches are direly needed. In particular, much research in recent years showed that GBM cells can obtain a highly plastic and dynamic phenotype, which gives these cells a stem-like state that enables them to out-live conventional therapies and ultimately replenish the tumor. In order to collectively present and aggregate recent developments in precision oncology, we invite both original research and review articles highlighting key aspects of glioblastoma biology, with a special focus on stem-like cells.

Dr. Benedikt Linder
Dr. Ander Matheu
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 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. Cancers 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 2900 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

  • brain cancer
  • glioblastoma
  • glioma
  • precision medicine
  • stem-like cells
  • treatment resistance
  • tumor recurrence
  • targeted therapy
  • precision oncology

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Published Papers (2 papers)

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Research

22 pages, 7073 KiB  
Article
Nuclear Glycoprotein A Repetitions Predominant (GARP) Is a Common Trait of Glioblastoma Stem-like Cells and Correlates with Poor Survival in Glioblastoma Patients
by Niklas Zimmer, Emily R. Trzeciak, Andreas Müller, Philipp Licht, Bettina Sprang, Petra Leukel, Volker Mailänder, Clemens Sommer, Florian Ringel, Jochen Tuettenberg, Ella Kim and Andrea Tuettenberg
Cancers 2023, 15(24), 5711; https://doi.org/10.3390/cancers15245711 - 5 Dec 2023
Cited by 1 | Viewed by 1590
Abstract
Glioblastoma (GB) is notoriously resistant to therapy. GB genesis and progression are driven by glioblastoma stem-like cells (GSCs). One goal for improving treatment efficacy and patient outcomes is targeting GSCs. Currently, there are no universal markers for GSCs. Glycoprotein A repetitions predominant (GARP), [...] Read more.
Glioblastoma (GB) is notoriously resistant to therapy. GB genesis and progression are driven by glioblastoma stem-like cells (GSCs). One goal for improving treatment efficacy and patient outcomes is targeting GSCs. Currently, there are no universal markers for GSCs. Glycoprotein A repetitions predominant (GARP), an anti-inflammatory protein expressed by activated regulatory T cells, was identified as a possible marker for GSCs. This study evaluated GARP for the detection of human GSCs utilizing a multidimensional experimental design that replicated several features of GB: (1) intratumoral heterogeneity, (2) cellular hierarchy (GSCs with varied degrees of self-renewal and differentiation), and (3) longitudinal GSC evolution during GB recurrence (GSCs from patient-matched newly diagnosed and recurrent GB). Our results indicate that GARP is expressed by GSCs across various cellular states and disease stages. GSCs with an increased GARP expression had reduced self-renewal but no alterations in proliferative capacity or differentiation commitment. Rather, GARP correlated inversely with the expression of GFAP and PDGFR-α, markers of astrocyte or oligodendrocyte differentiation. GARP had an abnormal nuclear localization (GARPNU+) in GSCs and was negatively associated with patient survival. The uniformity of GARP/GARPNU+ expression across different types of GSCs suggests a potential use of GARP as a marker to identify GSCs. Full article
(This article belongs to the Special Issue Targeting Human Glioblastoma Stem-Like Cells (GSCs))
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22 pages, 7054 KiB  
Article
Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells
by Sarah Rehbein, Anna-Lena Possmayer, Süleyman Bozkurt, Catharina Lotsch, Julia Gerstmeier, Michael Burger, Stefan Momma, Claudia Maletzki, Carl Friedrich Classen, Thomas M. Freiman, Daniel Dubinski, Katrin Lamszus, Brett W. Stringer, Christel Herold-Mende, Christian Münch, Donat Kögel and Benedikt Linder
Cancers 2023, 15(21), 5249; https://doi.org/10.3390/cancers15215249 - 31 Oct 2023
Cited by 1 | Viewed by 1394
Abstract
Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease [...] Read more.
Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis. These and other factors are hypothesized to be largely due to the fact that glioblastoma cells are known to be able to obtain stem-like traits, thereby driving these phenotypes. Recently, we have shown that the in vitro and ex vivo treatment of glioblastoma stem-like cells with the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2-vitamin D3) can block stemness in a subset of cell lines and reduce tumor growth. Here, we expanded our cell panel to over 40 different cultures and can show that, while half of the tested cell lines are sensitive, a quarter can be classified as high responders. Using genetic and proteomic analysis, we further determined that treatment success can be partially explained by specific polymorphism of the vitamin D3 receptor and that high responders display a proteome suggestive of blockade of stemness, as well as migratory potential. Full article
(This article belongs to the Special Issue Targeting Human Glioblastoma Stem-Like Cells (GSCs))
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