Targeting Bioinformatics Predicted Biomarkers Associated with Cell Proliferation and Migration for Treating Gliomas: Preclinical Studies in a GL261 Mouse Model

Neuroglia

article

Rheal A. Towner¹  Nataliya Smith²  Debra Saunders²  Megan Lerner⁴  Randy L. Jensen⁵  James Battiste³  Marya Ahmed¹  Jonathan D. Wren⁶ 

[1] Department of Chemistry, University of Prince Edward Island;Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation;Department of Neurosurgery, Stephenson Cancer Center, University of Oklahoma Health Sciences Center;Department of Surgery Research Laboratory, University of Oklahoma Health Sciences Center;Huntsman Cancer Institute, University of Utah;Genes & Human Disease Research Program, Oklahoma Medical Research Foundation

关键词: high-grade glioma (HGG);    GL261;    antibody therapies;    Plexin-B2;    SLIT-3;    Spondin-1;    molecular-targeted MRI (mt-MRI);    bioinformatics;    Ki67;    CD44;   

DOI  :  10.3390/neuroglia4010006

学科分类：医学解剖学

来源: mdpi

【 摘 要 】

We previously reported on the experimental validation of several in silico-predicted glioma biomarkers (e.g., Plexin-B2 (PLXNB2), SLIT3, and Spondin-1 (SPON1)) that were found to be higher in human high-grade gliomas (HGGs). In this study, we validated their therapeutic potential by investigating antibody therapies against these three biomarkers in a preclinical mouse GL261 high-grade glioma model. Efficacies for antibody therapies against these biomarkers were assessed by survival and tumor volumes, biomarker expressions, cell invasion and proliferation, and bioinformatics gene/protein associations. Antibodies against PLXNB2, SLIT3, or SPON1 were effective in significantly reducing tumor volumes and increasing animal survival. With immunohistochemistry (IHC), these biomarkers were highly expressed in human HGGs, as well as in mice tumors. From IHC, CD44v6 was significantly decreased for all three antibody treatments, compared to UT GL261 tumors. Bioinformatics suggested that targeting either PLXNB2 or SPON1 may have a major effect on HGG cell migration and invasion (validated with CD44v6 IHC), whereas targeting SLIT3, in addition to affecting cell invasion, may also affect cell proliferation (not validated with Ki67 IHC). These results indicate that targeting these three biomarkers could add to the therapeutic arsenal against high-grade gliomas and that antibodies against them could be considered for clinical translation.

【 授权许可】

CC BY