COX/mPGES-1/PGE sub( 2) pathway depicts an inflammatory-dependent high-risk neuroblastoma subset

The majority of solid tumors are presented with an inflammatory microenvironment. Proinflammatory lipid mediators including prostaglandin E... (PGE...) contribute to the establishment of inflammation and have been linked to tumor growth and aggressiveness. Here we show that high-risk neuroblastoma w...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-06, Vol.112 (26), p.8070-8070
Main Authors: Larsson, Karin, Kock, Anna, Idborg, Helena, Henriksson, Marie Arsenian, Martinsson, Tommy, Johnsen, John I, Korotkova, Marina, Kogner, Per, Jakobsson, Per-Johan
Format: Article
Language:English
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Summary:The majority of solid tumors are presented with an inflammatory microenvironment. Proinflammatory lipid mediators including prostaglandin E... (PGE...) 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 PGE... 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 PGE... 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 PGE... 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. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0027-8424