Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.

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 contribu...

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Autores principales:	Jelena Põlajeva, Anna M Sjösten, Nina Lager, Marianne Kastemar, Ida Waern, Irina Alafuzoff, Anja Smits, Bengt Westermark, Gunnar Pejler, Lene Uhrbom, Elena Tchougounova
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a4c64c7d8ce4eb480c4e3f3b9142361
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spelling	oai:doaj.org-article:2a4c64c7d8ce4eb480c4e3f3b91423612021-11-04T06:08:15ZMast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.1932-620310.1371/journal.pone.0025222https://doaj.org/article/2a4c64c7d8ce4eb480c4e3f3b91423612011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21949886/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Glioblastoma 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.Jelena PõlajevaAnna M SjöstenNina LagerMarianne KastemarIda WaernIrina AlafuzoffAnja SmitsBengt WestermarkGunnar PejlerLene UhrbomElena TchougounovaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e25222 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jelena Põlajeva Anna M Sjösten Nina Lager Marianne Kastemar Ida Waern Irina Alafuzoff Anja Smits Bengt Westermark Gunnar Pejler Lene Uhrbom Elena Tchougounova Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.
description	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.
format	article
author	Jelena Põlajeva Anna M Sjösten Nina Lager Marianne Kastemar Ida Waern Irina Alafuzoff Anja Smits Bengt Westermark Gunnar Pejler Lene Uhrbom Elena Tchougounova
author_facet	Jelena Põlajeva Anna M Sjösten Nina Lager Marianne Kastemar Ida Waern Irina Alafuzoff Anja Smits Bengt Westermark Gunnar Pejler Lene Uhrbom Elena Tchougounova
author_sort	Jelena Põlajeva
title	Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.
title_short	Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.
title_full	Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.
title_fullStr	Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.
title_full_unstemmed	Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.
title_sort	mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine cxcl12.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/2a4c64c7d8ce4eb480c4e3f3b9142361
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Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12.

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