Are there attacking points in the eicosanoid cascade for chemotherapeutic options in benign meningiomas?

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>The current treatment for recurrent or malignant meningiomas with adjuvant therapies has not been satisfactory, and there is an intense interest in evaluating new molecular markers to act as therapeutic targets. Enzymes of the arachidonic acid (AA) cascade such as cyclooxygenase (COX)–2 or 5-lipoxygenase (5-LO) are upregulated in a number of epithelial tumors, but to date there are hardly any data about the expression of these markers in meningiomas. To find possible targets for chemotherapeutic intervention, the authors evaluated the expression of AA derivatives at different molecular levels in meningiomas.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>One hundred and twenty-four meningioma surgical specimens and normal human cortical tissue samples were immunohistochemically and cytochemically stained for COX-2, COX-1, 5-LO, and prostaglandin E receptor 4 (PTGER4). In addition, Western blot and polymerase chain reaction (PCR) analyses were performed to detect the presence of eicosanoids in vivo and in vitro.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Sixty (63%) of 95 benign meningiomas, 21 (88%) of 24 atypical meningiomas, all five malignant meningiomas, and all normal human cortex samples displayed high COX-2 immunoreactivity. All cultured specimens and IOMM-Lee cells stained positive for COX-2, COX-1, 5-LO, and PTGER4. The PCR analysis demonstrated no changes in eicosanoid expression among meningiomas of different World Health Organization grades and in normal human cortical and dura mater tissue.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Eicosanoid derivatives COX-1, COX-2, 5-LO, and PTGER4 enzymes show a high universal expression in meningiomas but are not upregulated in normal human cortex and dura tissue. This finding of the ubiquitous presence of these enzymes in meningiomas offers an excellent baseline for testing upcoming chemotherapeutic treatments.</jats:p></jats:sec>

Genes Encoding Enzymatic Activities Implicated in the Eicosanoid Cascade of Arachidonic Acid and their Receptors are Expressed at mRNA Levels in Human Meningiomas

“…Results indicated the following rank of magnitude in human meningiomas: 5-LOX> 15-LOX1 >> 15-LOX2 > 12-LOX. Results of the present study, thus, confirm the presence of 5-LOX in human meningiomas and that 5-LOX levels did not significantly differ among different WHO grades (Pfister et al, 2007). Beside 5-LOX, we highlight for the first time the presence of 15-LOX and 12-LOX transcripts in meningiomas.…”

“…We did not find a relationship between COX-2 transcript levels and the tumor grade in meningiomas. This putative link remains a conflicting question since studies documented it (Pistolesi et al, 2007;Panagopoulos et al, 2008) while others did not (Linn et al, 2003;Buccoliero et al, 2007;Pfister et al, 2007). Nevertheless the ubiquitous expression of COX-2 in meningioma tumors may suggest considering COX-2 inhibitors as a potential area of therapeutic intervention.…”

“…The existence of COX and 5-LOX enzymes and high levels of AA in meningiomas create a favorable environment for the efficient production of eicosanoids (Boado et al, 1992;Nathoo et al, 2004;Pfister et al, 2007). Thus TXB 2 , PGE 2 and PGI 2 are produced in meningiomas (Castelli et al, 1989).…”

Immune cell infiltration and inflammatory landscape in primary brain tumours

“…Nevertheless, in the astrocytoma cohort we found 5-LOX expression to be significantly and positively correlated to TG2. Interestingly, both enzymes modulate the inflammation pathway, probably also with the activation of the NF-κB pathway [22,87]. Among gliomas, astrocytomas showed a significant reduction in the levels of CD3 + and CD4 + lymphocytes when compared to GBM.…”

An observational study on the expression of cyclooxygenase-2 in meningioma

“…Pfister and colleagues in their study on 124 meningioma surgical specimens and normal human cortical tissue samples found high COX-2 immunoreactivity in 100%, 88%, and 63% of malignant, atypical, and benign meningiomas, respectively, but not in normal human cortex and dura tissue. [21] A study by Lee et al . on 88 specimens of meningioma showed a correlation between COX-2 expression and the recurrence and invasiveness of meningioma.…”