1. Academic Validation
  2. Tenascin-cmediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

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

  • Cell Death Dis. 2019 Nov 21;10(12):879. doi: 10.1038/s41419-019-2102-3.
Hai-Ping Cai 1 Jing Wang 1 Shao-Yan Xi 2 Xiang-Rong Ni 1 Yin-Sheng Chen 1 Yan-Jiao Yu 1 Zi-Wen Cen 1 Zhi-Hui Yu 1 Fu-Rong Chen 1 Cheng-Cheng Guo 1 Ji Zhang 1 Chao Ke 1 Jian Wang 1 Zhong-Ping Chen 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P.R. China.
  • 2 Department of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P.R. China.
  • 3 Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P.R. China. [email protected].
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.

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