Artikel
Tumor (stem) cell-derived Tenascin-W is primarily found in the perivascular niche of primary glioblastomas
Suche in Medline nach
Autoren
Veröffentlicht: | 28. April 2011 |
---|
Gliederung
Text
Objective: Among the extracellular matrix (ECM) proteins enriched in gliomas, the tenascin family plays an outstanding role in tumorigenesis and neoangiogenesis and, moreover, impacts patient outcome. Recently, Tenascin-W (TN-W) was identified as a novel member of the tenascin family that exhibits a perivascular staining pattern in glioblastoma (GBM) tissue. In this analysis, we sought to determine the source of TN-W expression and its WHO grade-dependent expression pattern in gliomas.
Methods: Tissue sections of normal brain, WHO grade II and III astrocytomas, and secondary and primary GBMs (n=50) were stained immunohistochemically with monoclonal antibodies against human TN-W or the endothelial cell marker CD31. After slide digitalization, the expression was quantified by a Bayes classifier using Visiopharm image analysis software. Additionally, TN-W mRNA and protein levels were determined by LightCycler qPCR and Western Blot in cultures of adult neural progenitor cells (NPCs), different sources of endothelial cells (HUVECs, HMECs and tumor-derived endothelial cells) as well as GBM-derived adherent tumor cells and tumor stem cells (TSCs).
Results: In astrocytomas of all WHO grades, TN-W staining was predominantly localized to the perivascular space even though not every CD31+ blood vessel stained for TN-W. No TN-W staining was detected in normal brain. Most interestingly, TN-W expression was low in WHO grade II and III astrocytomas and secondary GBMs and did not increase concurrently with the WHO-grade dependent rise in CD31+ blood vessels. In contrast, a strong perivascular TN-W expression was found in primary GBMs. Of cellular origin, TN-W mRNA and protein expression were detected primarily in NPC and TSC and to a lesser extent in adherent tumor cell cultures, whereas endothelial cell cultures exhibited only marginal expression levels.
Conclusions: Cellular origin and staining pattern in tumor tissues suggest a contribution of TN-W to the perivascular tumor stem cell niche of primary glioblastoma. Since TN-W is not expressed in normal brain, it might emerge as a promising therapeutic target in primary GBM.