Molecular and cell biology of brain tumor stem cells: lessons from neural progenitor/stem cells

2008 ◽  
Vol 24 (3-4) ◽  
pp. E25 ◽  
Author(s):  
Zhigang Xie ◽  
Lawrence S. Chin
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Cell Fate ◽  
Cell Biology ◽  
Neural Progenitor ◽  
Tumor Stem Cells ◽  
Tumor Initiating Cells ◽  
Brain Tumor Stem Cells

✓ The results of studies conducted in the past several years have suggested that malignant brain tumors may harbor a small fraction of tumor-initiating cells that are likely to cause tumor recurrence. These cells are known as brain tumor stem cells (BTSCs) because of their multilineage potential and their ability to self-renew in vitro and to recapitulate original tumors in vivo. The understanding of BTSCs has been greatly advanced by knowledge of neural progenitor/stem cells (NPSCs), which are multipotent and self-renewing precursor cells for neurons and glia. In this article, the authors summarize evidence that genetic mutations that deregulate asymmetric cell division by affecting cell polarity, spindle orientation, or cell fate determinants may result in the conversion of NPSCs to BTSCs. In addition, they review evidence that BTSCs and normal NPSCs may reside in similar vascularized microenvironments, where similar evolutionarily conserved signaling pathways control their proliferation. Finally, they discuss preliminary evidence that mechanisms of BTSC-associated infiltrativeness may be similar to those underlying the migration of NPSCs and neurons.

scholarly journals EGFR blockade in GBM brain tumor stem cells synergizes with JAK2/STAT3 pathway inhibition to abrogate compensatory mechanisms in vitro and in vivo

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Katharine V Jensen ◽  
Xiaoguang Hao ◽  
Ahmed Aman ◽  
H Artee Luchman ◽  
Samuel Weiss
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Compensatory Mechanism ◽  
Tumor Stem Cells ◽  
Egfr Inhibition ◽  
Stat3 Signaling ◽  
Brain Tumor Stem Cells ◽  
Xenograft Models

Abstract Background The EGFR pathway is frequently mutated in glioblastoma (GBM). However, to date, EGFR therapies have not demonstrated efficacy in clinical trials. Poor brain penetration of conventional inhibitors, lack of patient stratification for EGFR status, and mechanisms of resistance are likely responsible for the failure of EGFR-targeted therapy. We aimed to address these elements in a large panel of molecularly diverse patient-derived GBM brain tumor stem cells (BTSCs). Methods In vitro growth inhibition and on-target efficacy of afatinib, pacritinib, or a combination were assessed by cell viability, neurosphere formation, cytotoxicity, limiting dilution assays, and western blotting. In vivo efficacy was assessed with mass spectrometry, immunohistochemistry, magnetic resonance imaging, and intracranial xenograft models. Results We show that afatinib and pacritinib decreased BTSC growth and sphere-forming capacity in vitro. Combinations of the 2 drugs were synergistic and abrogated the activation of STAT3 signaling observed upon EGFR inhibition in vitro and in vivo. We further demonstrate that the brain-penetrant EGFR inhibitor, afatinib, improved survival in EGFRvIII mt orthotopic xenograft models. However, upregulation of the oncogenic STAT3 signaling pathway was observed following afatinib treatment. Combined inhibition with 2 clinically relevant drugs, afatinib and pacritinib, synergistically decreased BTSC viability and abrogated this compensatory mechanism of resistance to EGFR inhibition. A significant decrease in tumor burden in vivo was observed with the combinatorial treatment. Conclusions These data demonstrate that brain-penetrant combinatorial therapies targeting the EGFR and STAT3 signaling pathways hold therapeutic promise for GBM.

scholarly journals Overlapping migratory mechanisms between neural progenitor cells and brain tumor stem cells

2019 ◽  
Vol 76 (18) ◽  
pp. 3553-3570 ◽  
Author(s):  
Natanael Zarco ◽  
Emily Norton ◽  
Alfredo Quiñones-Hinojosa ◽  
Hugo Guerrero-Cázares
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

Brain Tumor Stem Cells: Bringing Order to the Chaos of Brain Cancer

2008 ◽  
Vol 26 (17) ◽  
pp. 2916-2924 ◽  
Author(s):  
Peter B. Dirks
Keyword(s):  
Stem Cell ◽  
Brain Tumor ◽  
Cell Biology ◽  
In Vivo Models ◽  
Brain Tumor Cells ◽  
Brain Tumor Stem Cells ◽  
New Treatments ◽  
Key Pathways

Brain tumors are generally incurable cancers. Work from a number of laboratories strongly suggests that they are organized as a hierarchy based on a subset of cancer cells that have stem-cell properties. These cells have now been shown to be resistant to conventional therapy and responsive to differentiation therapy. New in vitro and in vivo models for interrogating brain tumor cells in stem-cell conditions have been developed that provide important new opportunities for elucidating the key pathways responsible for driving the proliferation of these cells. Continued application of the principles of stem-cell biology to the study of brain cancers is likely to continue to bring further important insight into these aggressive cancers, bringing new treatments and understanding of the origins.

scholarly journals Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions

2010 ◽  
Vol 12 (12) ◽  
pp. 1220-1230 ◽  
Author(s):  
Einar Osland Vik-Mo ◽  
Cecilie Sandberg ◽  
Havard Olstorn ◽  
Mercy Varghese ◽  
Petter Brandal ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Stem Cells ◽  
Serum Free ◽  
Brain Tumor Stem Cells ◽  
Serum Free Conditions

Isolation and identification of brain tumor stem cells within tumors of human neuroepithelial tissue in vitro

2008 ◽  
Vol 32 (3) ◽  
pp. S26-S26
Author(s):  
Jia Sheng Fang ◽  
Yong Wen Deng ◽  
Ming Chu Li ◽  
Feng Hua Chen ◽  
Ming Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Stem Cells ◽  
Isolation And Identification ◽  
Brain Tumor Stem Cells

In Vitro Self-Renewal Assays for Brain Tumor Stem Cells

2018 ◽  
pp. 79-84 ◽  
Author(s):  
Mathieu Seyfrid ◽  
David Bobrowski ◽  
David Bakhshinyan ◽  
Nazanin Tatari ◽  
Chitra Venugopal ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Stem Cells ◽  
Self Renewal ◽  
Brain Tumor Stem Cells

scholarly journals Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Valentina Caldera ◽  
Marta Mellai ◽  
Laura Annovazzi ◽  
Angela Piazzi ◽  
Michele Lanotte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genetic Alterations ◽  
Tumor Stem Cells ◽  
Primary Tumors ◽  
Immunodeficient Mice ◽  
Brain Tumor Stem Cells ◽  
Tumor Phenotype ◽  
Fetal Bovine ◽  
Primary Glioblastomas

Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self-renewal, clonogenic capacities, and tumorigenicity following transplantation into immunodeficient mice, may denounce the existence of brain tumor stem cells (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS showed the same genetic alterations as primary tumors and the expression of stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum (FBS) to the culture, were genetically different from NS and prevailingly expressed differentiation antigens. NS developed from a highly malignant tumor phenotype with proliferation, circumscribed necrosis, and high vessel density. Beside originating from transformed neural stem cells (NSCs), BTSCs may be contained within or correspond to dedifferentiated cells after mutation accumulation, which reacquire the expression of stemness antigens.

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