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Intravital imaging reveals local effects of biopsy on glioma cell migration

Alieva M, Colak B, Van Rheenen J.


Targeting the migratory capacity of tumor cells to stop infiltration into normal parenchyma is one of the main challenges in glioma treatment. It has been shown that alternations of the local tumor microenvironment can drive the migratory behavior of cells. Common clinical interventions such as a biopsy are source of environment alteration; howeve its local effects on cancer cell behavior are surprisingly unknown. In this study we imaged with single-cell resolution the behavior of glioma cells in living mice and evaluated the change in tumor migratory capacity upon biopsy.
C57BL/6 mice were injected orthotopically with H2B-Dendra2 expressing Gl261 cells under a cranial imaging window. Upon formation of a solid tumor, repeated intravital imaging was used to quantify speed of individual cells over several hours and assess the effect of a biopsy-like injury on tumor migratory capacity. Additionally, Dendra2 photoconversion approach was used to evaluate the invasion of groups of cells over several days.
Our results showed that 24 hours after biopsy there was a 1.76 fold increase in migratory cells compared to the control group (p<0.0001). Interestingly, immune suppression by dexamethasone treatment decreased tumor cell motility and prevented this biopsy-induced increase of tumor cell migration. Although we observed these local effects, we did not find evidence for enhanced tumor cell invasion into normal parenchyma 1 week after the injury suggesting that the migration potentiating effect is localized to the biopsied site.
Our data suggests that external interventions such as a biopsy can potentiate locally glioma migratory capacity. Anti-inflammatory treatment modulates the biopsy-induced migration. Although no effect on tumor cell spreading was detected at long term, our data suggests that more intravital imaging studies are required to evaluate the effects of more invasive interventions such as surgery and chemotherapy treatment.

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