Glioblastoma aggression and spread predicted by new assay

Written by Lauren Pulling

Researchers from John Hopkins Medicine (MD, USA) have developed an assay that has the potential to determine the aggression and rate of spread of glioblastoma tumors. This information could enable clinicians to make more informed treatment choices and provide patients with a more accurate prognosis than is currently possible.
Alfredo Quinones-Hinojosa, John Hopkins University School of Medicine (MD, USA), explained: “After I remove a brain tumor from a patient, the patient always asks me, ‘Doc, how long do I have?’ I don’t have a reliable way to answer them. But we have taken a step to creating a possible way to provide useful updates, inform treatment choices and perhaps develop new treatments faster.”

At present, only 3–5% of glioblastoma patients survive 5 years after diagnosis, making it one of the most aggressive cancers. The new test, published in Cell Reports, tracks the movement of chemically-primed glioblastoma cells from surgically removed tumors along a glass slide – this allows the researchers to determine the migratory patterns of different tumor types. This migration mimics that which occurs during the initial stages of glioblastoma and leads to brain cancer invasion.

The researchers demonstrated that those cells that moved the fastest along the glass slide paralleled the quicker disease progression of 14 glioblastoma patients. While the team highlight that further studies are required to confirm these observations, the assay represents a promising new method that could be used in the clinical environment to determine the nature of glioblastoma tumors in individual patients.

Unlike genetic or protein-based tests, the new ‘racetrack’ assay may be able to predict migration rates, and consequently survival time, for glioblastoma patients. The racetrack test comprises an engineered glass slide with small parallel ridges along its length that mimic those in the brain.

Glioblastoma cells were encouraged to migrate via the application of platelet-derived growth factor (PDGF), which is known to stimulate growth in gliomas. When compared against a control group, the team observed that the fastest 25% of tumor cells responded to PDGF stimulation by moving twice as fast as untreated glioblastoma control cells. Conversely, the slowest 25% of cells moved at the same pace as untreated controls, indicating that PDGF has a stronger effect on faster cells.

“We learned from this experiment that we couldn’t take the average of the fast and slow cells from each tumor because that would mask differences in the speedy outliers,” commented Quinones-Hinojosa. “We had to pay attention to the cells moving very fast because these are the really bad cells that we believe are going to cause the tumor to spread.”

Furthermore, the scientists grew glioblastoma cells from 14 patients in PDGF. Importantly, they observed that the five patients with the fastest growing tumors had recurrence of glioblastoma within six months. Conversely, the six patients with slower tumor cells had no recurrence between 6–22 months.

This study indicates that the test could enable clinicians to predict the aggression and rate of spread of glioblastomas. While the results of the assay must yet be confirmed by further and larger studies, the researchers are hopeful that the new method could lead to more informed treatment choices and the faster development of new treatments.

Sources: Smith CL, Kilic O, Schiapparelli P et al. Migration phenotype of brain-cancer cells predicts patient outcomes. Cell Reports doi:10.1016/j.celrep.2016.05.042 (2016) (In press corrected proof); www.hopkinsmedicine.org/news/media/releases/cellular_racetrack_accurately_clocks_brain_cancer_cell_movementglio