Functional significance of VEGF-a in human ovarian carcinoma: role in vasculogenic mimicry.
Ovarian cancer is a silent killer, and shows early extensive tumor invasion and peritoneal metastasis. The microcirculation of most tumors includes cooperation of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis and vasculogenic mimicry (VM). VM is critical for a tumor blood supply and is asscociated with aggressive features and metastasis. Our studies highlight the plasticity of aggressive human ovarian carcinoma cells and call into question the underlying significance of their ability to form VM in vitro induced by VEGF-a. These studies also show their clinicalpathological features of the cancers with human Paraffin-embedded tumor tissue samples. Results show that the process: VEGF-a-->EphA2-->MMPs-->VM is the main pathway for VM formation and VEGF-a appears to play an important role in the formation of VM based on our in vitro assays and clinical immunohistochemical analyses. VM-targeting strategies for ovarian cancer include anti-VEGF-a treatment, knocking down the EphA2 gene and using antibodies against human MMPs if the tumor is VM positive. This strategy may be of significant value in laying the foundation for a more explicit anti-tumor angiogenesis therapy.
Wang
Jun-Yan
JY
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.
Sun
Tao
T
Zhao
Xiu-Lan
XL
Zhang
Shi-Wu
SW
Zhang
Dan-Fang
DF
Gu
Qiang
Q
Wang
Xing-Hui
XH
Zhao
Nan
N
Qie
Shuo
S
Sun
Bao-Cun
BC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D014945:Wound Healing
D019408:Platelet Endothelial Cell Adhesion Molecule-1