P04.39 Tenascin-c expression correlates to vasculogenic mimicry formation and predicts a poor prognosis in glioblastoma. (19th September 2018)

• Record Type: Journal Article
• Authors: Cai, H; Chen, Y; Ni, X; Chen, Z
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 3
• Page Start: iii287
• Page End: iii288
• Publication Date: 2018-09-19
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy139.273
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Glioblastoma is a highly invasive and vascularized primary CNS tumor and the effect of anti-angiogenesis therapy on glioblastoma is not as adequate yet. Vasculogenic mimicry (VM), a vessel-like structure formed by highly invasive tumor cells, has been considered as one of reasons to failure from anti-angiogenesis therapy for GBM patients. Tenascin-c (TNC), an extracellular protein overexpressed in glioblastoma, may stimulate angiogenesis in tumor. However, whether TNC contributes to VM formation remains unclear. Material and Methods: Fifty tumor samples from glioblastoma patients were evaluated for VM formation and TNC expression by Immunohistochemistry staining. The results were compared with prognosis of the patients. Tenascin-c expressions were also examined for glioma cell lines, U251, A172, U373, U138 and LN308 by western blotting analysis, and the results were compared with the VM formation ability evaluated by three-dimensional culture assay. The direct effect of TNC on VM formation of glioma cell lines were investigated by exogenous tenascin-c exposure. Results: Tenascin-c positive stainings were found in 54% (27/50) of GBM samples, while VM channels were determined in 34% (17/50) of GBM samples. Tenascin-c expression was significantly higher in VM positive group (15/17) than in the VM negative group (12/33; χ 2 =12.154, P<0.01). Of glioblastoma samples with TNC overexpression, the levels of microvessel density were 25.55 ± 7.03, which was higher than that in TNC low expression samples (13.22 ± 5.34, p<0.01). The patients with TNC overexpression or VM positive in their tumors exhibited worse survival time (median overall survival TNC high : 12 months vs. median overall survival TNC low : 20 months; p=0.011 and median overall survival VM positive : 12 months vs. median overall survival VM negative : 17 months; p=0.0041). Glioma cell lines U251 and A172 had high tenascin-c expression (relative expression: 2.01 and 1.38), while U373, LN308 and U138 had low tenascin-c expression (relative expression: 0.05, 0.32 and 0.72). Three-dimensional culture assay showed that U251 and A172 formed more classical vessel-like structures (vessel number: 91.67 ± 2.87 and 76.67 ± 4.99), in contrast with U373, LN308 and U138, which formed open brand-like structures (vessel number: 2.33 ± 0.47, 0.67 ± 0.47 and 2.67 ± 0.94). After stimulated by exogenous tenascin-c (10mg/ml) for six hours in U373, LN308 and U138, the number of closed vessel-like structure increased (vessel number: 24.67 ± 2.05, 6.33 ± 1.25 and 17.67 ± 3.09). Conclusion: Our results indicate that tenascin-c overexpression may contribute to vaccinogenic mimicry formation and relate to poor prognosis of glioblastoma patients. This study was supported by grants from the National Natural Science Funds of China (No. 81372685)