Fibulin-5 inhibits the cell proliferation, migration and angiogenesis in glioma

Glioma, especially the high-grade glioma, is the most common primary brain malignant tumor, with extremely poor prognosis. Angiogenesis has been demonstrated to play a crucial role in the growth and metastasis of glioma. Fibulin-5 is a multifunctional extracellular matrix (ECM) protein that mediates cell-cell and cell-matrix communication. Recent evidence has suggested that Fibulin-5 is involved in angiogenesis and tumor metastasis. However, the exact role of Fibulin-5 in glioma remains largely unclear. In the present study, immunohistochemical staining data showed the positive expression rate of Fibulin-5 in the normal brain tissues and low grade glioma were higher than that in high grade glioma. Moreover, the expression level of Fibulin-5 was inversely correlated with microvessel density, and Ki-67 and HIF-1α expression in human glioma tissues. We further studied the role of Fibulin-5 in the regulation of biological functions of vessel endothelial cells and glioma cells in vitro. Overexpression of Fibulin-5 significantly suppressed cell proliferation via inducing a cell cycle arrest at G1 phase in HUVEC-2C cells. Moreover, Fibulin-5 upregulation also enhanced the cell adhesion, while inhibited the migration and vessel-sprouting capacities of HUVEC-2C cells. Furthermore, co-culture of glioma U251 cells and Fibulin-5-transfected HUVEC-2C cells significantly suppressed the proliferation, migration and invasion of U251 cells. In summary, we suggest that Fibulin-5 acts as a tumor suppressor in glioma, through inhibition of vessel formation within the microenvironment of tumor tissues.