Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.

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Brain tumor stem cells and the tumor microenvironment

Neurosurgical FOCUS ◽

10.3171/foc/2008/24/3-4/e26 ◽

2008 ◽

Vol 24 (3-4) ◽

pp. E27 ◽

Cited By ~ 9

Author(s):

Rahul Jandial ◽

Hoisang U ◽

Michael L. Levy ◽

Evan Y. Snyder

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Brain Tumor ◽

Cancer Stem Cells ◽

Tumor Stem Cells ◽

Tumor Environment ◽

Brain Tumor Stem Cells ◽

Differentiation And Proliferation ◽

The Brain

✓ Recent advances in stem cell research and developmental neurobiology have uncovered new perspectives from which to investigate various forms of cancer. Specifically, the hypothesis that tumors consist of a subpopulation of malignant cells similar to stem cells is of great interest to scientists and clinicians and has been dubbed the “cancer stem cell hypothesis.” The region in which this assertion is most relevant is within the brain. Cancer stem cells have been isolated from brain tumors that exhibit characteristics of differentiation and proliferation normally seen only in neural stem cells. These cancer stem cells may be responsible for tumor origin, survival, and proliferation. Furthermore, these cells must be considered within their immediate microenvironment when investigating mechanisms of tumorigenesis. Evidence of brain tumor stem cells is reviewed along with the role of tumor environment as the context within which these cells should be understood.

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Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽

10.3390/cancers13071674 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1674

Author(s):

Sara Tomei ◽

Ola Ibnaof ◽

Shilpa Ravindran ◽

Soldano Ferrone ◽

Cristina Maccalli

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Immune Responses ◽

Antigen Processing ◽

Aberrant Expression ◽

Immunological Profile ◽

Malignant Lesions ◽

Novel Therapeutic Strategies ◽

Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

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The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽

10.3390/cancers13061239 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1239

Author(s):

Leila Jahangiri ◽

Tala Ishola ◽

Perla Pucci ◽

Ricky M. Trigg ◽

Joao Pereira ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Progression ◽

Regulatory Networks ◽

Epithelial To Mesenchymal Transition ◽

Tumour Microenvironment ◽

Repair Capacity ◽

Mesenchymal Transition ◽

Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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Role of p38γ MAPK in regulation of EMT and cancer stem cells

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2018.08.024 ◽

2018 ◽

Vol 1864 (11) ◽

pp. 3605-3617 ◽

Cited By ~ 12

Author(s):

Mei Xu ◽

Siying Wang ◽

Yongchao Wang ◽

Huaxun Wu ◽

Jacqueline A. Frank ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells

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The role of steroid hormones in breast cancer stem cells

Endocrine Related Cancer ◽

10.1530/erc-15-0350 ◽

2015 ◽

Vol 22 (6) ◽

pp. T177-T186 ◽

Cited By ~ 21

Author(s):

Bruno M Simões ◽

Denis G Alferez ◽

Sacha J Howell ◽

Robert B Clarke

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Steroid Hormones ◽

Normal Mammary Gland ◽

Breast Cancer Stem Cells ◽

Tumor Initiating Cells ◽

Unit Of Selection ◽

Selection For

Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity.

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