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Mast Cell Accumulat...
Mast Cell Accumulation in Glioblastoma with a Potential Role for Stem Cell Factor and Chemokine CXCL12
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- Põlajeva, Jelena (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Sjösten, Anna M (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Lager, Nina (author)
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- Kastemar, Marianne (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Waern, Ida (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
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- Alafuzoff, Irina (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Smits, Anja (author)
- Uppsala universitet,Institutionen för neurovetenskap,neurologi
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- Westermark, Bengt (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Pejler, Gunnar (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
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- Uhrbom, Lene (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Tchougounova, Elena (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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(creator_code:org_t)
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- 2011-09-19
- 2011
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9
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Abstract
Subject headings
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- Glioblastoma multiforme (GBM) is the most common and malignant form of glioma with high mortality and no cure. Many human cancers maintain a complex inflammatory program triggering rapid recruitment of inflammatory cells, including mast cells (MCs), to the tumor site. However, the potential contribution of MCs in glioma has not been addressed previously. Here we report for the first time that MCs infiltrate KRas+Akt-induced gliomas, using the RCAS/TV-a system, where KRas and Akt are transduced by RCAS into the brains of neonatal Gtv-a- or Ntv-a transgenic mice lacking Ink4a or Arf. The most abundant MC infiltration was observed in high-grade gliomas of Arf-/- mice. MC accumulation could be localized to the vicinity of glioma-associated vessels but also within the tumor mass. Importantly, proliferating MCs were detected, suggesting that the MC accumulation was caused by local expansion of the MC population. In line with these findings, strong expression of stem cell factor (SCF), i.e. the main MC growth factor, was detected, in particular around tumor blood vessels. Further, glioma cells expressed the MC chemotaxin CXCL12 and MCs expressed the corresponding receptor, i.e. CXCR4, suggesting that MCs could be attracted to the tumor through the CXCL12/CXCR4 axis. Supporting a role for MCs in glioma, strong MC infiltration was detected in human glioma, where GBMs contained significantly higher MC numbers than grade II tumors did. Moreover, human GBMs were positive for CXCL12 and the infiltrating MCs were positive for CXCR4. In conclusion, we provide the first evidence for a role for MCs in glioma.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Molecular medicine (genetics and pathology)
- Molekylär medicin (genetik och patologi)
Publication and Content Type
- ref (subject category)
- art (subject category)
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PLOS ONE
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- By the author/editor
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Põlajeva, Jelena
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Sjösten, Anna M
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Lager, Nina
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Kastemar, Marian ...
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Waern, Ida
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Alafuzoff, Irina
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show more...
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Smits, Anja
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Westermark, Beng ...
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Pejler, Gunnar
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Uhrbom, Lene
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Tchougounova, El ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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PLOS ONE
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Uppsala University
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Swedish University of Agricultural Sciences