Vasculogenic mimicry (VM) is different from classical
tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various
cancers. Canstatin was first identified as an endogenous
angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human
glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in
Matrigel. A xenograft
glioma model was created by
subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of
glioma xenografts. In
tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related
VEGF (
vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of
Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of
glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.