2023-03-07 デューク大学(Duke)
この新しい方法は、脳腫瘍の治療法の開発に寄与することが期待される。また、脳腫瘍に対する新しい治療法の開発が求められている。これらの研究結果は、『Pharmaceutics』に掲載された。
<関連情報>
- https://www.nottingham.ac.uk/news/brain-tumour-discovery-paves-way-for-new-drug-treatments
- https://www.mdpi.com/1999-4923/15/2/599
高悪性度神経膠腫における低密度リポ蛋白質経路は、ナノ治療薬の送達に適したユビキタスな代謝脆弱性である。 Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery
Adenike O. Adekeye,David Needham and Ruman Rahman
Pharmaceutics Published: 10 February 2023
DOI:https://doi.org/10.3390/pharmaceutics15020599
Abstract
Metabolic reprogramming, through increased uptake of cholesterol in the form of low-density lipoproteins (LDL), is one way by which cancer cells, including high grade gliomas (HGG), maintain their rapid growth. In this study, we determined LDL receptor (LDLR) expression in HGGs using immunohistochemistry on tissue microarrays from intra- and inter tumour regions of 36 adult and 133 paediatric patients to confirm LDLR as a therapeutic target. Additionally, we analysed expression levels in three representative cell line models to confirm their future utility to test LDLR-targeted nanoparticle uptake, retention, and cytotoxicity. Our data show widespread LDLR expression in adult and paediatric cohorts, but with significant intra-tumour variation observed between the core and either rim or invasive regions of adult HGG. Expression was independent of paediatric tumour grade or identified clinicopathological factors. LDLR-expressing tumour cells localized preferentially within perivascular niches, also with significant adult intra-tumour variation. We demonstrated variable levels of LDLR expression in all cell lines, confirming their suitability as models to test LDLR-targeted nanotherapy delivery. Overall, our study reveals the LDLR pathway as a ubiquitous metabolic vulnerability in high grade gliomas across all ages, amenable to future consideration of LDL-mediated nanoparticle/drug delivery to potentially circumvent tumour heterogeneity.
