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COX/mPGES-1/PGE2 pa...
COX/mPGES-1/PGE2 pathway depicts an inflammatory-dependent high-risk neuroblastoma subset
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- Larsson, K. (författare)
- Karolinska Institutet
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- Kock, A. (författare)
- Karolinska Institutet
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- Idborg, H. (författare)
- Karolinska Institutet
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- Arsenian Henriksson, M. (författare)
- Karolinska Institutet
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- Martinsson, Tommy, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics
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- Johnsen, J. I. (författare)
- Karolinska Institutet
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- Korotkova, M. (författare)
- Karolinska Institutet
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- Kogner, P. (författare)
- Karolinska Institutet
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- Jakobsson, P. J. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2015-06-15
- 2015
- Engelska.
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:26, s. 8070-8075
- Relaterad länk:
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https://www.pnas.org...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The majority of solid tumors are presented with an inflammatory microenvironment. Proinflammatory lipid mediators including prostaglandin E2 (PGE2) contribute to the establishment of inflammation and have been linked to tumor growth and aggressiveness. Here we show that high-risk neuroblastoma with deletion of chromosome 11q represents an inflammatory subset of neuroblastomas. Analysis of enzymes involved in the production of proinflammatory lipid mediators showed that 11q-deleted neuroblastoma tumors express high levels of microsomal prostaglandin E synthase-1 (mPGES-1) and elevated levels of PGE2. High mPGES-1 expression also corresponded to poor survival of neuroblastoma patients. Investigation of the tumor microenvironment showed high infiltration of tumor-promoting macrophages with high expression of the M2-polarization markers CD163 and CD206. mPGES-1-expressing cells in tumors from different subtypes of neuroblastoma showed differential expression of one or several cancer-associated fibroblast markers such as vimentin, fibroblast activation protein alpha, alpha smooth muscle actin, and PDGF receptor beta. Importantly, inhibition of PGE2 production with diclofenac, a nonselective COX inhibitor, resulted in reduced tumor growth in an in vivo model of 11q-deleted neuroblastoma. Collectively, these results suggest that PGE2 is involved in the tumor microenvironment of specific neuroblastoma subgroups and indicate that therapeutic strategies using existing anti-inflammatory drugs in combination with current treatment should be considered for certain neuroblastomas.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
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