uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mast Cells Are Recruited to Glioma and Orchestrate Cancer Cell Invasion
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology. (B. Westermark)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
National Category
Immunology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-180248OAI: oai:DiVA.org:uu-180248DiVA: diva2:548866
Available from: 2012-09-01 Created: 2012-09-01 Last updated: 2013-01-23
In thesis
1. Glioma as an Ecosystem: Studies of Invasion, Onco-miR Addiction and Mast Cell Infiltration
Open this publication in new window or tab >>Glioma as an Ecosystem: Studies of Invasion, Onco-miR Addiction and Mast Cell Infiltration
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite recent advances in oncology and extensive research efforts, gliomas remain essentially incurable. Glioblastoma multiforme (GBM, WHO grade IV) is the most common glioma and may arise de novo or progress from a lower-grade lesion. GBM is characterized by invasive growth, aberrant angiogenesis and necrosis. The heterogeneity of GBM is further complicated by the contribution of the inflammation that is facilitated by immune cells that reside in and infiltrate this immuno-privileged organ.

One of the cells types present in the tumor microenvironment are mast cells (MC) that accumulate in the tumor in a grade-dependent manner. GBM cells secrete a plethora of cytokines acting as chemoattractants in MC recruitment and to a lesser degree induce MC proliferation in situ. Expression of one of the cytokines secreted by GBM cells - macrophage migration inhibitory factor (MIF) - correlates with MC accumulation in vivo.

GBM cells invade the surrounding parenchyma making complete resection impossible. Here, migration was studied with the focus on RAP1 and its negative regulator RAP1GAP. Activation of RAP1 signaling by lentiviral silencing of RAP1GAP lead to decrease in cell migration and a shift in expression of SOX2 and GFAP, presumably enhancing stem cell phenotype.

MicroRNAs are small non-coding RNAs known to regulate the mRNA network. miR-21 is highly overexpressed in the majority of cancers including GBM. Its expression is strictly regulated during embryonic development of the brain. SOX2 is co-regulated with miR-21 demarcating a cell population with neural/glial progenitor/stem cell properties. In an experimental mouse model, expression of miR-21 can be sustained by forced expression of PDGF-BB leading to gliomagenesis. GBM cells seem to be addicted to oncogenic properties of miR-21 as its knockdown leads to extensive apoptosis. This observation combined with the fact that miR-21 is absent in the normal adult mammalian brain suggest miR-21 to be an excellent therapeutic target.

Effects of conventional therapy (surgery combined with radiochemotherapy) on prolonging patient survival have reached a plateau. New effective personalized therapeutic modalities need to be designed and implemented. Targeting the tumor microenvironment as well as cell intrinsic properties like invasive potential, stemness and onco-miR addiction studied in this thesis will hopefully lead to efficient disruption of GBM’s aberrant ecosystem.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 53 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 806
Keyword
glioblastoma, mast cell, miR-21, RAP1, CXCL12, SOX2
National Category
Biochemistry and Molecular Biology Cell Biology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-180249 (URN)978-91-554-8456-9 (ISBN)
Public defence
2012-10-12, Rudbecksalen, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-09-21 Created: 2012-09-01 Last updated: 2013-01-23Bibliographically approved

Open Access in DiVA

No full text

By organisation
Cancer and Vascular BiologyDepartment of Immunology, Genetics and Pathology
ImmunologyBiochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 421 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf