Expression of multidrug-resistance P-glycoprotein (MDR1) in human brain tumors

Abstract

Multidrug resistance (MDR) is associated with the expression of P-glycoprotein (P-gp), an ATP-dependent transporter which expels anti-cancer drugs from cells. In the present study, MDR1 P-gp was immunodetected by Western blot analysis in 60 human brain tumors, including meningiomas, schwannomas, low-grade gliomas (astrocytomas, pilocytic astrocytomas) and high-grade gliomas (anaplastic astrocytomas, glioblastomas and anaplastic oligodendrogliomas). Most samples from primary tumors expressed P-gp at the same levels as normal brain tissue except for schwannomas, in which levels were reduced by 65%, and meningiomas, in which levels were more than 10-fold higher in 7 of 10 samples. P-gp levels were 70% and 95% lower in brain metastases from melanomas and lung adenocarcinomas, respectively, than in normal brain tissue. These results indicate that the majority of primary brain tumors express MDR1 P-gp and that its high expression levels in meningiomas may be a marker for this type of brain tumor.

Induction of HSF1 expression is associated with sporadic colorectal cancer

“…The reverse association of MDR1 expression with HSF1 and β-catenin (Wnt pathway) indicated that different signal pathways contributed to the carcinogenesis of FAP and sporadic CRC. The reduced MDR1 gene expression was also found in other cancers such as kidney cancer [33] and brain cancer [34] . Recently, a large number of studies have revealed the association of iNOS expression with various cancers [35][36][37][38][39] .…”

Randomized Study of Paclitaxel and Tamoxifen Deposition into Human Brain Tumors: Implications for the Treatment of Metastatic Brain Tumors

“…Demeule et al found that tumor and vasculature P-glycoprotein expression by Western blot in gliomas was similar to that in normal brain tissue, whereas P-glycoprotein levels in brain metastases from lung adenocarcinomas and melanoma were 40% and 5% of that in normal brain tissue, respectively (37). Furthermore, tumor and its neovasculature from concordant primary lung adenocarcinomas and its brain metastases had low and equal P-glycoprotein immunohistochemistry expression, suggesting the P-glycoprotein levels in MBT reflect P-glycoprotein expression in the tissue of origin (37).…”

“…Demeule et al found that tumor and vasculature P-glycoprotein expression by Western blot in gliomas was similar to that in normal brain tissue, whereas P-glycoprotein levels in brain metastases from lung adenocarcinomas and melanoma were 40% and 5% of that in normal brain tissue, respectively (37). Furthermore, tumor and its neovasculature from concordant primary lung adenocarcinomas and its brain metastases had low and equal P-glycoprotein immunohistochemistry expression, suggesting the P-glycoprotein levels in MBT reflect P-glycoprotein expression in the tissue of origin (37). Together, findings suggest significantly decreased P-glycoprotein immunohistochemistry expression in MBT and its neovasculature compared with PBT (36,37) and suggest that the BBB-MDR phenotype in PBT is mediated to a minor degree by tumor cells and predominantly at the level of tumor BBB vasculature.…”

“…Furthermore, tumor and its neovasculature from concordant primary lung adenocarcinomas and its brain metastases had low and equal P-glycoprotein immunohistochemistry expression, suggesting the P-glycoprotein levels in MBT reflect P-glycoprotein expression in the tissue of origin (37). Together, findings suggest significantly decreased P-glycoprotein immunohistochemistry expression in MBT and its neovasculature compared with PBT (36,37) and suggest that the BBB-MDR phenotype in PBT is mediated to a minor degree by tumor cells and predominantly at the level of tumor BBB vasculature. Conversely, MBT generally have low P-glycoprotein expression in their tumor cells and vasculature dependent upon histologic origin (34 -37).…”

“…Because there is concordance of P-glycoprotein expression in the vasculature of tumors and their brain metastases (36,37), this concept may be relevant for tumors which commonly metastasize to the brain and have low intrinsic P-glycoprotein expression in its tumor cells and neovasculature, such as NSCLC, SCLC, melanoma, and NPC-sensitive breast cancers. The current treatment paradigm for MBT with chemotherapy is not well established.…”