التفاصيل البيبلوغرافية
| العنوان: |
JAM-A functions as a female microglial tumor suppressor in glioblastoma |
| المؤلفون: |
Soumya M. Turaga, Tyler J. Alban, Joshua B. Rubin, Daniel J. Silver, Ruth A. Keri, Jill S. Barnholtz-Sloan, Adam Lauko, Sen Peng, Nozha Borjini, James R. Connor, Sarah Stanko, Justin D. Lathia, Defne Bayik, Ulhas P. Naik, Dimitrios Davalos, Evi Paouri, Michael E. Berens |
| المصدر: |
Neuro Oncol |
| بيانات النشر: |
Cold Spring Harbor Laboratory, 2019. |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Male, Genetically modified mouse, Cancer Research, education, Brain tumor, Context (language use), Biology, 03 medical and health sciences, 0302 clinical medicine, In vivo, Cancer stem cell, Glioma, medicine, Humans, Genes, Tumor Suppressor, Cell adhesion, 030304 developmental biology, Regulation of gene expression, Sex Characteristics, 0303 health sciences, Tumor microenvironment, Microglia, Cell adhesion molecule, Cell growth, fungi, medicine.disease, Phenotype, In vitro, humanities, medicine.anatomical_structure, Oncology, Basic and Translational Investigations, Cancer research, Female, Neurology (clinical), Glioblastoma, 030217 neurology & neurosurgery |
| الوصف: |
Background Glioblastoma (GBM) is the most aggressive primary brain tumor and has a dismal prognosis. Previously, we identified that junctional adhesion molecule A (JAM-A), a cell adhesion molecule, is highly elevated in human GBM cancer stem cells and predicts poor patient prognosis. While JAM-A is also highly expressed in other cells in the tumor microenvironment, specifically microglia and macrophages, how JAM-A expression in these cells affects tumor growth has yet to be determined. The goal of this study was to understand the role of microenvironmental JAM-A in mediating GBM growth. Methods Male and female wild-type (WT) and JAM-A–deficient mice were transplanted intracranially with the syngeneic glioma cell lines GL261 and SB28 and were assessed for differences in survival and microglial activation in tumors and in vitro. RNA-sequencing was performed to identify differentially regulated genes among all genotypes, and differences were validated in vitro and in vivo. Results We found that JAM-A–deficient female mice succumbed to GBM more quickly compared with WT females and JAM-A–deficient and male WT mice. Analysis of microglia in the tumors revealed that female JAM-A–deficient microglia were more activated, and RNA-sequencing identified elevated expression of Fizz1 and Ifi202b specifically in JAM-A–deficient female microglia. Conclusions Our findings suggest that JAM-A functions to suppress pathogenic microglial activation in the female tumor microenvironment, highlighting an emerging role for sex differences in the GBM microenvironment and suggesting that sex differences extend beyond previously reported tumor cell–intrinsic differences. |
| اللغة: |
English |
| DOI: |
10.1101/761445 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0a0a2e581389510c9e5e4c65a6edbbc |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....b0a0a2e581389510c9e5e4c65a6edbbc |
| قاعدة البيانات: |
OpenAIRE |