Glioblastoma Factors Increase the Migration of Human Brain Endothelial Cells In Vitro by Increasing MMP-9/CXCR4 Levels

Abstract

Background/aim: Glioblastoma (GB) is the most aggressive type of tumor in the central nervous system and is characterized by resistance to therapy and abundant vasculature. Tumor vessels contribute to the growth of GB, and the tumor microenvironment is thought to influence tumor vessels. We evaluated the molecular communication between human GB cells and human brain microvascular endothelial cells (HBMEC) in vitro.

Materials and methods: We investigated whether GB-conditioned media (GB-CM) influenced HBMEC proliferation and migration, as well as the levels of MMP-9, CXCL12, CXCR4, CXCR7, VEGFs, VEGFR-2, and WNT5a in HBMEC.

Results: Although HBMEC proliferation was not modified, increased HBMEC migration was detected after GB-CM treatment. Furthermore, treatment of HBMEC with GB-CM resulted in increased levels of MMP-9 and CXCR4. The levels of WNT5a, VEGFs and VEGFR-2 were not affected.

Conclusion: GB-secreted factors lead to increased endothelial cell migration and to increased levels of MMP-9 and CXCR4.

Keywords: Angiogenesis; CXCR4; MMP-9; cell crosstalk; endothelial cells; glioblastoma.