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Reactive astrocytes potentiate tumor aggressiveness in a murine glioma resection and recurrence model
- Source :
- Neuro-Oncology. 18:1622-1633
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
Abstract
- Background Surgical resection is a universal component of glioma therapy. Little is known about the postoperative microenvironment due to limited preclinical models. Thus, we sought to develop a glioma resection and recurrence model in syngeneic immune-competent mice to understand how surgical resection influences tumor biology and the local microenvironment. Methods We genetically engineered cells from a murine glioma mouse model to express fluorescent and bioluminescent reporters. Established allografts were resected using image-guided microsurgery. Postoperative tumor recurrence was monitored by serial imaging, and the peritumoral microenvironment was characterized by histopathology and immunohistochemistry. Coculture techniques were used to explore how astrocyte injury influences tumor aggressiveness in vitro. Transcriptome and secretome alterations in injured astrocytes was examined by RNA-seq and Luminex. Results We found that image-guided resection achieved >90% reduction in tumor volume but failed to prevent both local and distant tumor recurrence. Immunostaining for glial fibrillary acidic protein and nestin showed that resection-induced injury led to temporal and spatial alterations in reactive astrocytes within the peritumoral microenvironment. In vitro, we found that astrocyte injury induced transcriptome and secretome alterations and promoted tumor proliferation, as well as migration. Conclusions This study demonstrates a unique syngeneic model of glioma resection and recurrence in immune-competent mice. Furthermore, this model provided insights into the pattern of postsurgical tumor recurrence and changes in the peritumoral microenvironment, as well as the impact of injured astrocytes on glioma growth and invasion. A better understanding of the postsurgical tumor microenvironment will allow development of targeted anticancer agents that improve surgery-mediated effects on tumor biology.
- Subjects :
- 0301 basic medicine
Cancer Research
Transcriptome
Mice
03 medical and health sciences
0302 clinical medicine
Basic and Translational Investigation
Cell Movement
Cell Line, Tumor
Glioma
Tumor Microenvironment
Animals
Medicine
Cell Proliferation
Tumor microenvironment
Glial fibrillary acidic protein
biology
Brain Neoplasms
business.industry
Nestin
Allografts
medicine.disease
Coculture Techniques
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Oncology
Astrocytes
030220 oncology & carcinogenesis
Cancer research
biology.protein
Immunohistochemistry
Neurology (clinical)
Neoplasm Recurrence, Local
Glioblastoma
business
Immunostaining
Astrocyte
Subjects
Details
- ISSN :
- 15235866 and 15228517
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....8a9a179e88bc4826f3582b55a718ede0