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Advances in Cancer Stem Cells
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Advances in Cancer Stem Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 12426

Special Issue Editors

Prof. Dr. Fritz Mertzlufft

E-Mail Website
Guest Editor
Protestant Hospital of Bethel Foundation, University Medical School OWL at Bielefeld University, Campus Bielefeld-Bethel, Maraweg 21, D-33617 Bielefeld, Germany
Interests: stem cells; oxygen; inflammation; clinical physiology; critical care; emergency medicine
Prof. Dr. Christian Kaltschmidt

E-Mail Website
Guest Editor
Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany
Interests: cancer stem cells; signal transduction; MYC; NF-kappaB; immunotherapy; TNF; IL1; EMT; inflammation

Special Issue Information

Dear Colleagues,

Cancer stem cells (CSCs) have been a medical subject term in the U.S. National Library of Medicine since 2008 (neoplastic stem cells). CSCs are characterized as highly proliferative, self-renewing cells, which can form colonies and give rise to neoplasms. Therapy for most neoplasms starts with surgical removal of the neoplasm forming a malignant tumor. Frequently, residual cancer cells including CSCs are treated by additional chemo- and/or immunotherapy. CSCs with changes like epithelial-mesenchymal transition (EMT) are seen as the main reason for the formation of metastasis, but mostly escape current treatments due to their quiescent status and metabolism with high resistance to chemotherapy and immune escape mechanisms. Here, we will review CSCs in a bottom-up approach starting from tumor surgery to cell biology of CSCs and discuss advances in understanding signaling pathways. These might include Notch, WNT, Hedgehog, and the Hippo pathway. Furthermore, inflammation-related signaling impinging on transcription factors like NF-kappaB or MYC will be discussed. Similarities and differences of CSCs from different organs such as the brain, lung, reproductive tract, and digestive system will be taken into account. Advancements of CSCs within precision medicine will be reviewed, with cultured CSCs as a potential screening system for drug treatment, complementing surgery.

We would like to invite you to contribute reviews and/or original work for a Special Issue on “Advances in Cancer Stem Cells”. It would be a pleasure to receive a contribution from you.

Prof. Dr. Fritz Mertzlufft
Prof. Dr. Christian Kaltschmidt
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • cancer stem cells
  • tumor-initiating cells
  • neoplastic stem cells
  • chemotherapy
  • immunotherapy
  • WNT
  • Notch
  • NF-kappaB
  • MYC
  • EMT

Published Papers (3 papers)

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Research

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25 pages, 8658 KiB  
Article
Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA
by Kaya E. Witte, Jesco Pfitzenmaier, Jonathan Storm, Melanie Lütkemeyer, Clara Wimmer, Wiebke Schulten, Nele Czaniera, Marvin Geisler, Christine Förster, Ludwig Wilkens, Cornelius Knabbe, Fritz Mertzlufft, Barbara Kaltschmidt, Jan Schulte am Esch and Christian Kaltschmidt
Int. J. Mol. Sci. 2021, 22(16), 8901; https://doi.org/10.3390/ijms22168901 - 18 Aug 2021
Cited by 8 | Viewed by 2745
Abstract
Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell [...] Read more.
Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors. Full article
(This article belongs to the Special Issue Advances in Cancer Stem Cells)
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Review

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15 pages, 980 KiB  
Review
Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?
by Constanze Banz-Jansen, Laureen P. Helweg and Barbara Kaltschmidt
Int. J. Mol. Sci. 2022, 23(6), 3412; https://doi.org/10.3390/ijms23063412 - 21 Mar 2022
Cited by 17 | Viewed by 5067
Abstract
Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial [...] Read more.
Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial Cancer Stem Cells (CSC) might be drivers of carcinogenesis as well as metastatic and recurrent disease. Therefore, targeting CSCs is of high interest to improve prognosis of patients suffering of advanced or recurrent endometrial cancer. This review describes the current evidence of molecular mechanisms in endometrial CSCs with special emphasis on MYC and NF-κB signaling as well as mitochondrial metabolism. Furthermore, the current status of immunotherapy targeting PD-1 and PD-L1 in endometrial cancer cells and CSCs is elucidated. The outlined findings encourage novel therapies that target signaling pathways in endometrial CSCs as well as immunotherapy as a promising therapeutic approach in the treatment of endometrial cancer to impede cancer progression and prevent recurrence. Full article
(This article belongs to the Special Issue Advances in Cancer Stem Cells)
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18 pages, 1544 KiB  
Review
Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy
by Virinder Kaur Sarhadi, Ravindra Daddali and Riitta Seppänen-Kaijansinkko
Int. J. Mol. Sci. 2021, 22(20), 11035; https://doi.org/10.3390/ijms222011035 - 13 Oct 2021
Cited by 32 | Viewed by 4023
Abstract
Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic [...] Read more.
Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy. Full article
(This article belongs to the Special Issue Advances in Cancer Stem Cells)
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