Format

Send to

Choose Destination
Int J Radiat Oncol Biol Phys. 2018 Aug 29. pii: S0360-3016(18)33639-3. doi: 10.1016/j.ijrobp.2018.08.033. [Epub ahead of print]

Late Effects of Radiation Prime the Brain Microenvironment for Accelerated Tumor Growth.

Author information

1
Department of Chemistry, Washington University, Saint Louis, Missouri, United States.
2
Department of Radiology, Washington University, Saint Louis, Missouri, United States; Department of Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
3
Department of Neurosurgery, Washington University, Saint Louis, Missouri, United States.
4
Department of Radiology, Washington University, Saint Louis, Missouri, United States.
5
Department of Radiation Oncology, Washington University, Saint Louis, Missouri, United States.
6
Department of Neurosurgery, Washington University, Saint Louis, Missouri, United States; Department of Radiation Oncology, Washington University, Saint Louis, Missouri, United States.
7
Department of Neuropathology, Washington University, Saint Louis, Missouri, United States.
8
Department of Medicine, Washington University, Saint Louis, Missouri, United States.
9
Department of Chemistry, Washington University, Saint Louis, Missouri, United States; Department of Radiology, Washington University, Saint Louis, Missouri, United States; Department of Medicine, Washington University, Saint Louis, Missouri, United States; Alvin J Siteman Cancer Center, Washington University, Saint Louis, Missouri, United States.
10
Department of Radiology, Washington University, Saint Louis, Missouri, United States; Alvin J Siteman Cancer Center, Washington University, Saint Louis, Missouri, United States. Electronic address: garbow@wustl.edu.

Abstract

PURPOSE:

Glioblastoma (GBM) remains incurable, despite state-of-the-art treatment involving surgical resection, chemotherapy, and radiation. GBM invariably recurs as a highly invasive and aggressive phenotype, with the majority of recurrences within the radiotherapy treatment field. While a large body of literature reporting on primary GBM exists, comprehensive studies of how prior irradiation alters recurrent tumor growth are lacking. An animal model that replicates the delayed effects of radiotherapy on the brain microenvironment and its impact on the development of recurrent GBM would be a significant advance.

METHODS AND MATERIALS:

Cohorts of mice received a single-fraction of 0, 20, 30, or 40 Gy Gamma Knife irradiation, respectively. Naïve, non-irradiated mouse glioblastoma tumor cells (DBT) were implanted into the ipsilateral hemisphere six weeks post-irradiation. Tumor growth was measured by magnetic resonance imaging (MRI) and animal survival was assessed by monitoring weight loss. MRI results were supported by H&E histology.

RESULTS:

Tumorous lesions generated from orthotopic implantation of non-irradiated mouse glioblastoma tumor cells into irradiated mouse brain grew far more aggressively and invasively than implantation of these same cells into non-irradiated brain. Lesions in irradiated brain tissue were significantly larger, more necrotic, and more vascular than those in control animals with increased invasiveness of tumor cells in the periphery, consistent with the histologic features commonly observed in recurrent high-grade tumors in patients.

CONCLUSIONS:

Irradiation of normal brain primes the targeted cellular micro-environment for aggressive tumor growth when naïve (not previously irradiated) cancer cells are subsequently introduced. The resultant growth-pattern is similar to the highly aggressive pattern of tumor regrowth observed clinically following therapeutic radiotherapy. The mouse model offers an avenue for determining the cellular and molecular basis for the aggressiveness of recurrent GBM.

KEYWORDS:

Glioblastoma; Microenvironment; Radiation Effect; Recurrent Tumor

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center