The Reactive Astrocytes After Surgical Brain Injury Potentiates the Migration, Invasion, and Angiogenesis of C6 Glioma

Abstract

Surgical resection is a key method for glioma treatment. This inherently invasive procedure alters the tumor microenvironment of glioma cells that cannot be removed by surgery. However, few studies have focused on the impact of this microenvironment change on the growth of glioma cells. The authors preconstructed a surgical brain injury model, and then C6 glioma cells were transplanted. HE staining was used to observe the general morphology of tumor cells, and immunohistochemistry of MMP-2, MMP-9, GFAP, and CD31 was used to evaluate the invasiveness of glioma cells and activation of astrocytes and calculate microvessel density. Invitro, primary rat astrocytes were exposed to different temperature gradients. The supernatant was made into conditioned medium for culturing C6 glioma cells. The scratch test and transwell test were used to evaluate the migration and invasion of tumor cells. GFAP expression was stronger in surgical brain injury rats, C6 cells implanted in these rats showed stronger expression of MMP-2 and MMP-9, and CD31 was expressed in more microvessels. Astrocytes exposed to high temperatures of 40°C and 43°C expressed stronger GFAP, and C6 cells cultured in their supernatants had stronger scratch healing ability and the ability to cross transwell chambers. The microenvironment changes caused by surgical brain injury will enhance the migration and invasion of glioma cells and increase the microvessel density in the tumor. This effect may be related to the activation of astrocytes caused by the thermal injury of bipolar coagulation during surgery.