Tenascin-cmediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma.

Abstract

Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser473 and Thr308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

• Authors: Hai-Ping Cai, Jing Wang, Shao-Yan Xi, Xiang-Rong Ni, Yin-Sheng Chen, Yan-Jiao Yu, Zi-Wen Cen, Zhi-Hui Yu, Fu-Rong Chen, Cheng-Cheng Guo, Ji Zhang, Chao Ke, Jian Wang, Zhong-Ping Chen
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 12 Pg. 879 (11 21 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 31754182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heterocyclic Compounds, 3-Ring
• MK 2206
• TNC protein, human
• Tenascin
• Proto-Oncogene Proteins c-akt
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Animals
• Apoptosis (physiology)
• Brain Neoplasms (blood supply, enzymology, metabolism)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Female
• Glioma (blood supply, enzymology)
• Heterocyclic Compounds, 3-Ring (pharmacology)
• Heterografts
• Humans
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplasm Grading
• Neovascularization, Pathologic (enzymology, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Tenascin (biosynthesis, metabolism)
• Up-Regulation