Bengt Westermark – Human malignant glioma – from oncogenic mechanisms to treatment
Our research is focused on glioblastoma, which is the most common malignant adult brain tumor. The knowledge about molecular mechanisms involved in glioblastoma development has increased dramatically during the last decades. Despite this progress, the prognosis for glioblastoma patients remains poor, and new treatment modalities are needed in order to improve patient outcomes.
We study human glioma cells in culture, derived from fresh tumor tissue resected during brain tumor surgery. These cells serve as a tool to test different hypotheses in a controlled setting. The research centers around a growth factor (BMP4), a cell cycle inhibitor (p21), and a transcription factor (SOX2), crucial regulators in glioblastoma biology governing stemness, differentiation, and growth control.
The role of SOX2
Project 1 focuses on developing a controllable system enabling studies of the role in SOX2 in glioblastoma. We analyze the effects of SOX2 gene knock-out on glioblastoma cell proliferation, gene expression, and tumor formation upon orthotopic transplantation in immune deficient mice. We also aim to develop efficacious SOX2 inhibitors in a drug development program. Preliminary findings suggest reduced tumorigenic potential in SOX2 knockout cells, indicating promising therapeutic avenues.
Regulation of cell size
Project 2 investigates cell size regulation in glioblastoma. Exposure of glioblastoma cells to BMP4 leads to an increase in cell size, mediated by p21. Mechanisms regulating the coordination between the cell cycle and cell growth have only been partially elucidated. We focus on identifying genes associated with cell size variation in glioblastoma cells. We leverage proteome data and conduct targeted CRISPR screens to identify candidate genes involved in cell size regulation.
Change in cell states
In project 3, we study single-cell-derived cultures (clones) from the same glioblastoma tumor sample (Segerman et al., Cell Reports, 2016). We find that the cancer cells naturally, but at low speed, can slide back and forth between more treatment-resistant (mesenchymal-like) and more treatment-sensitive (proneural-like) cell states. The project aims to identify regulatory mechanisms behind this spontaneous change in cell state and based on this knowledge find drugs/substances or combinations of these that induce the cell state linked to treatment sensitivity.
Publications
Tumor-specific migration routes of xenotransplanted human glioblastoma cells in mouse brain
Part of Scientific Reports, 2024
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Live Detection of Neural Progenitors and Glioblastoma Cells by an Oligothiophene Derivative
Part of ACS Applied Bio Materials, p. 3790-3797, 2023
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Tailoring vascular phenotype through AAV therapy promotes anti-tumor immunity in glioma
Part of Cancer Cell, p. 1134-1151, 2023
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A human cell type similar to murine central nervous system perivascular fibroblasts
Part of Experimental Cell Research, 2021
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Modeling glioblastoma heterogeneity as a dynamic network of cell states
Part of Molecular Systems Biology, 2021
Modeling glioblastoma heterogeneity as a dynamic network of cell states
Part of Molecular Systems Biology, 2021
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Part of Molecular Cancer Research, p. 981-991, 2020
BET and Aurora Kinase A inhibitors synergize against MYCN-positive human glioblastoma cells
Part of Cell Death and Disease, 2019
- DOI for BET and Aurora Kinase A inhibitors synergize against MYCN-positive human glioblastoma cells
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Part of Oncoimmunology, 2019
- DOI for Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors
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Part of Journal of Pathology, p. 295-307, 2019
Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis
Part of Journal of Internal Medicine, p. 16-44, 2018
Part of Acta Oncologica, p. 187-194, 2018
- DOI for U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
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Part of Cellular Signalling, p. 81-92, 2017
Part of Scientific Reports, 2016
- DOI for ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
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Case-specific potentiation of glioblastoma drugs by pterostilbene
Part of Oncotarget, p. 73200-73215, 2016
Part of Cell Reports, p. 2994-3009, 2016
- DOI for Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition
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Growth signals employ CGGBP1 to suppress transcription of Alu-SINEs
Part of Cell Cycle, p. 1558-1571, 2016
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Origin of the U87MG glioma cell line: Good news and bad news
Part of Science Translational Medicine, 2016
Simultaneous Multiplexed Measurement of RNA and Proteins in Single Cells
Part of Cell Reports, p. 380-389, 2016
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CGGBP1 mitigates cytosine methylation at repetitive DNA sequences
Part of BMC Genomics, 2015
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CGGBP1-an indispensable protein with ubiquitous cytoprotective functions
Part of Upsala Journal of Medical Sciences, p. 219-232, 2015
Part of European Journal of Pharmacology, p. 101-107, 2015
Part of Oncotarget, p. 23647-23661, 2015
- DOI for Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells
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Part of EBioMedicine, p. 1351-1363, 2015
- DOI for The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes
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CGGBP1 phosphorylation constitutes a telomere-protection signal
Part of Cell Cycle, p. 96-105, 2014
Part of Acta Physiologica, p. 100-100, 2014
Part of Molecular Oncology, p. 50-58, 2014
Platelet-derived growth factor in glioblastoma-driver or biomarker?
Part of Upsala Journal of Medical Sciences, p. 298-305, 2014
Selective Calcium Sensitivity in Immature Glioma Cancer Stem Cells
Part of PLOS ONE, 2014
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Taming the cancer cell: Introduction
Part of Journal of Internal Medicine, p. 2-4, 2014
Part of Cancer Medicine, p. 812-824, 2014
- DOI for U-251 revisited: genetic drift and phenotypic consequences of long-term cultures of glioblastoma cells
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Part of Cell, p. 313-328, 2014
Part of PLOS ONE, 2013
- DOI for Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures
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Part of Neuro-Oncology, p. 1469-1478, 2013
Evidence for multiple forms and modifications of human POT1
Part of DNA Repair, p. 876-877, 2013
Part of International Journal of Cancer, p. 1345-1356, 2013
Sox21 inhibits glioma progression in vivo by reducing Sox2 and stimulating aberrant differentiation
Part of International Journal of Cancer, p. 1345-1356, 2013
Part of Upsala Journal of Medical Sciences, p. 251-256, 2012
Part of European Journal of Cancer, 2012
miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma
Part of BMC Cancer, p. 378, 2012
- DOI for miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma
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CGGBP1 is a nuclear and midbody protein regulating abscission
Part of Experimental Cell Research, p. 143-150, 2011
CGGBP1 regulates cell cycle in cancer cells
Part of BMC Molecular Biology, p. 28, 2011
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Forced expression of Sox21 inhibits Sox2 and induces apoptosis in human glioma cells
Part of International Journal of Cancer, p. 45-60, 2011
Part of PLOS ONE, 2011
- DOI for Mast Cell Accumulation in Glioblastoma with a Potential Role for Stem Cell Factor and Chemokine CXCL12
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Part of Neoplasia, p. 492-503, 2011
Part of European Journal of Medical Genetics, p. 117-121, 2010
Part of PLoS ONE, 2009
Part of Oncogene, p. 3121-3131, 2009
Part of Glia, p. 1143-1153, 2009
Herbal melanin activates TLR4/NF-kappaB signaling pathway
Part of Phytomedicine, p. 477-84, 2009
Part of Oncogene, p. 1537-1548, 2009
Loss of Arf causes tumor progression of PDGFB-induced oligodendroglioma
Part of Oncogene, p. 6289-6296, 2007
Part of Molecular Cancer Research, p. 891-897, 2007
Part of Cancer Research, p. 8042-8048, 2006
Effect of herbal melanin on IL-8: a possible role of Toll-like receptor 4 (TLR4).
Part of Biochem Biophys Res Commun, p. 1200-6, 2006
Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis.
Part of Cancer Res, p. 2065-9, 2005
Part of Oncogene, p. 3896-3905, 2005
Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging
Part of Proceedings of the National Academy of Sciences of the United States of America, p. 11334-11337, 2004
Part of Cancer Research, p. 4305, 2003
Part of Glia, p. 276-89, 2003
Part of Development, Genes and Evolution, p. 476-487, 2003
Part of Brain Pathology, p. 165-175, 2003
TGF-alpha-driven tumor growth is inhibited by an EGF receptor tyrosine kinase inhibitor
Part of Biochemical and Biophysical Research Communications - BBRC, p. 349-58, 2002
A 1.8kb GFAP-promoter fragment is active in specific regions of theembryonic CNS
Part of Mechanisms of Development, p. 181-5, 2001
Part of Int J Cancer, p. 398-406, 2000
Epidermal growth factor receptor signaling activates Met in human anaplastic thyroid carcinoma cells
Part of Experimental Cell Research, p. 293-299, 2000
Part of Breast Cancer Research and Treatment, p. 197-210, 2000
Part of Int J Cancer, p. 819-828, 2000
Part of Int J Cancer, p. 211-222, 2000
Part of Endocrinology, p. 4300, 1999
Induction of brain tumors in mice using a recombinant PDGF B retrovirus
Part of Cancer Research, p. 5275-5279, 1998
Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members
Part of Biochemical and Biophysical Research Communications - BBRC, p. 505-11, 1998
Part of Mechanisms of Development, p. 167-180, 1998
Induction of senescence in human malignant glioma cells by p16INK4A
Part of Oncogene, p. 111, 1997
Part of Int J Cancer, p. 802-809, 1996
Part of Int J Cancer, p. 223-228, 1995
Luteal failure in transgenic mice carrying a PDGF dominant-negative mutant/GH hybrid transgene
Part of Transgenics (Basel. Print), p. 515-523, 1995
Part of Neuroscience Letters, p. 227-231, 1992
Part of American Journal of Pathology, p. 639-648, 1992
Part of Kidney International, p. 571-574, 1992
Part of EMBO Journal, p. 4121-4128, 1991
Part of Proceedings of the National Academy of Sciences of the United States of America, p. 8159-8163, 1991
Rat brain capillary endothelial cells express functional PDGF B-type receptors
Part of Growth Factors, p. 1-8, 1989
Part of Cell, p. 791-9, 1988