Circulating Brain Tumor Cells Discovered

Researchers have detected circulating tumor cells (CTCs) in patients with glioblastoma multiforme (GBM), an aggressive type of brain malignancy. Previously, brain tumor cells were thought to be confined to the brain and not to enter the blood circulation, but this may not be the case.

According to the study authors, this observation may be the reason why those individuals who receive an organ transplant from a glioblastoma multiforme patient may have post-transplant tumors develop outside of the brain. The brain tumor circulating cells could be a way to screen GBM as candidates for organ donation. The study was recently published in Science Translational Medicine.

“The findings by Müller et al. fracture the dogma that glioma cells survive only in the brain. The frequent presence of CTCs in the peripheral blood of GBM patients shows that these cells spread beyond the brain, an observation that has clinical implications for the use of organs from glioblastoma multiforme patients for transplantation,” wrote Lara Perryman and Janine T. Erler, of the Biotech Research and Innovation Centre and the University of Copenhagen in Denmark, in a perspective accompanying the study publication.

Carolin Müller, of the department of tumor biology at the University Medical Center Hamburg-Eppendorf, Germany and colleagues sought to detect CTCs in the peripheral blood of glioblastoma patients by immunostaining mononuclear cells with antibodies against a marker protein of glioblastoma multiforme cells. Of the 141 patient samples analyzed, these CTCs were detected in 20.6% (29) of patients. These cells were not detected in any samples from 23 healthy volunteers. The researchers could also detect epidermal growth factor receptor (EGFR) gene amplifications in these circulating cells, suggesting that they may have growth potential outside of the brain. EGFR abberations are frequently found in glioblastoma.

The number of CTCs varied from patient to patient, and was comparable to the numbers found in patients with other types of solid tumors.  The presence of these cells did not correlate with patients’ overall survival within a median of 17.3 months of follow-up.

To confirm that the CTCs detected were indeed tumor cells, the researchers sequenced both the CTC samples and the primary tumor cells from two patients which had similar chromosomal and gene aberrations.

GBM is the most common form of adult brain tumor. Patients with this central nervous system cancer have a median life expectancy ranging from only 12 to 15 months. The frequency of extracranial metastases among patients is less than 1%, and this low incidence has been previously attributed to various reasons including: restrictions of the blood-brain barrier, short survival duration of patients, suppression of extracranial tumor cells by the immune system, and the absence of lymphatic channels in the central nervous system.

The detection rate of extracranial tumors among those who receive an organ transplant from a glioblastoma patient is about 10% to 20%. “This incidence almost matches the CTC detection rate observed in the present study, suggesting that at least a subset of circulating glioblastoma cells might survive and home to a secondary organ, where their outgrowth might be controlled by the immune system,” noted the authors.

The mechanism of how glioblastoma cells end up in the peripheral blood circulation is not yet clear, nor is the clinical significance of the presence of these cells in the circulation. While no impact of survival was observed in this study, larger studies are needed to confirm this result.

According to Perryman and Erler, a limitation of the study is the biomarker used (glial fibrillary acidic protein), which is not expressed on all glioblastoma cells and therefore, the total number of CTCs may have been underestimated in the study.

Still, the perspective authors believe that CTCs could be used “to monitor response to therapy or progression of disease. Thus, the discovery of Müller et al. has the potential to affect the diagnosis, prognosis, and treatment of GBM patients,” they conclude.