Non-invasive quantification of brain tumor-induced astrogliosis.
BACKGROUND
CNS injury including stroke, infection, and tumor growth lead to astrogliosis, a process that involves upregulation of glial fibrillary acidic protein (GFAP) in astrocytes. However, the kinetics of astrogliosis that is related to these insults (i.e. tumor) is largely unknown.


RESULTS
Using transgenic mice expressing firefly luciferase under the regulation of the GFAP promoter (GFAP-luc), we developed a model system to monitor astrogliosis upon tumor growth in a rapid, non-invasive manner. A biphasic induction of astrogliosis was observed in our xenograft model in which an early phase of activation of GFAP was associated with inflammatory response followed by a secondary, long-term upregulation of GFAP. These animals reveal GFAP activation with kinetics that is in parallel with tumor growth. Furthermore, a strong correlation between astrogliosis and tumor size was observed.


CONCLUSIONS
Our results suggest that non-invasive, quantitative bioluminescent imaging using GFAP-luc reporter animal is a useful tool to monitor temporal-spatial kinetics of host-mediated astrogliosis that is associated with glioma and metastatic brain tumor growth.
Department of Surgery, University of California San Diego, San Diego, CA, USA.
Jisook
J
Lee
Alexandra K
AK
Borboa
Andrew
A
Baird
Brian P
BP
Eliceiri
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009367:Neoplasm Staging / Q000379:methods; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse; D049409:Luciferases, Firefly
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