Distribution pattern of Tenascin-C in glioblastoma: Correlation with angiogenesis and tumor cell proliferation

Abstract

Tenascin-C (TN-C) is an extracellular matrix protein which participates in different processes like normal fetal development, wound healing, inflammation, keloids and rheumatoid arthritis. Furthermore, the immunostaining for TN-C is seen in the stroma of various malignant tumors as in glioblastoma multiforme (GBM), however, the significance of these findings is still not clear. In this study 62 GBM samples were analyzed immunohistochemically for distribution patterns of TN-C and correlated with angiogenesis and tumor cell proliferation. Tenascin-C in GBM localizes in two compartments, perivascular and intercellular space. Intercellular tenascin-C (TN-C ic) showed focal distribution in 66%, and diffuse one in 34% of cases. Perivascular tenascin-C (TN-C pv) showed strong correlation with microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression. Moreover, it seems that TN-C pv enhanced the effect of VEGF. Intercellular TN-C did not correlate with MVD and VEGF expression, but showed strong correlation with proliferation index. Furthermore, tumors with diffuse TN-C ic expression had higher proliferation indices than tumors with focal TN-C expression. Our results indicate that TN-C plays a role in angiogenesis and tumor cell proliferation, but beside the intensity of expression, the distribution patterns are also important in these processes. This study also suggests that perivascular and intercellular TN-C compartments have probably different sources and different roles in GBM.

Comprehensive characterization of glioblastoma tumor tissues for biomarker identification using mass spectrometry-based label-free quantitative proteomics

“…These proteins are highly specific to GBM irrespective of their location in brain, thus providing important insights into the disease pathology as has been demonstrated by the validated proteins and their involvement in various events of tumorigenesis. Our analysis also provided several other upregulated proteins, like SERPH, PDIA1, CERU, TENA, VTNC, APOE, LEG1, HRG, and FKBP5, that are known to be involved in tumor progression, aggressiveness, and invasion in GBM (3,17,18,28,30,32,39,45,47). In addition to known GBM-associated proteins, novel potential biomarkers identified in this study include CLIC4, NP1L1, IGKC, TAGL2, and YES (Supplementary Table S1).…”

Eleven-Year Experience with the Avidin-Biotin Pretargeting System in Glioblastoma: Toxicity, Efficacy and Survival

“…Tenascin-C is expressed in more than 90% of gliomas and its expression increases with increasing tumor grade. Although its functions remain controversial, recent studies suggest that it plays a role in several cellular processes, including adhesion, migration and proliferation [23][24][25][26][27][28].…”

Role of tenascins in the ECM of gliomas

“…Tanaka et al discovered that TN-C regulates the expression of VEGF 85 and Behrem et al showed that TN-C has an influence on VEGF action and that the microvascular density shows a dependency of TN-C expression. 86 Additionally to the high expression of TN-C in glioma blood vessels the known receptor for TN-C, integrin a v, is found in elevated levels in glioma tissue, as well as the protein periostin. 77 Periostin was detected as a promoter of TN-C incorporation into the ECM and to organize the architecture of the ECM.…”