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.
Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including angiogenesis, cancer development, invasion and metastasis. The aim of the study was to analyze the expression of OPN in human astrocytomas and to correlate it with angiogenesis and patients' outcome. Seventy-six human astrocytomas including eight pilocytic astrocytomas (grade I), 10 diffuse astrocytomas (grade II), 8 anaplastic astrocytomas (grade III) and 50 glioblastomas (grade IV) were immunohistochemically stained for OPN protein. The distribution of OPN staining (cytoplasmic and/or interstitial) was assessed and compared to microvessel number and patients' survival. In normal brain tissue some glial and neuronal cells showed weak cytoplasmic staining, while interstitium was negative. Astrocytomas were heterogeneous regarding the OPN expression. High cytoplasmic OPN expression in glioblastomas was associated with poor patients' survival (p = 0.012). Also, we found the association of interstitial OPN expression and angiogenesis (p = 0.033), i.e. the number of newly formed blood vessels was higher in tumors showing high interstitial OPN expression. Our results indicate the overexpression of OPN protein in astrocytoma cells and suggest the role of OPN in astrocytoma progression and angiogenesis.
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