Artikel
Expression of alphavbeta3 integrin in gliomas is not restricted to tumor vasculature and correlates with tumor grade
Die Expression des Integrins alphavbeta3 ist in Gliomen nicht auf Tumorgefäße beschränkt und korreliert mit dem Tumorgrad
Suche in Medline nach
Autoren
Veröffentlicht: | 30. Mai 2008 |
---|
Gliederung
Text
Objective: The integrin alpha v beta 3 (αvβ3) has been appointed a key player in the angiogenesis of malignant gliomas. However, there is still a controversy about the expression and distribution of αvβ3 integrin dependent on malignancy. The aim of our study was to assess the extent and pattern of αvβ3 integrin expression within primary glioblastomas and low grade gliomas.
Methods: Immunohistochemical staining from tumor samples (GBM: n=12; LGG: n=4) for detection of αvβ3 integrin (clone LM609) were performed simultaneously and automatically to reach a maximum of accuracy. Staining was quantified by a special imaging software, which was calibrated for this purpose to xenotransplanted human melanoma cells (M21) expressing αvβ3. Within a selected area, we measured i) the mean intensity of the immunohistochemical staining and ii) the immunohistochemically positive fraction at distinct immunohistochemical staining intensities. To further analyze the distribution of the integrin subunits αv and β3, Western Blot analysis from corresponding histological sections (GBM: n=20; LGG: n=5), was performed. The microvascular distribution to αvβ3 expression in these tumors was determined by co-staining with endothelial cell specific markers (CD31).
Results: The expression of αvβ3 was found to be significantly higher in glioblastomas than in low grade gliomas. Focal strong reactivity was restricted to glioblastomas only. Moreover, Western Blot analysis demonstrated a significant difference in the expression of the β3-integrin subunit between glioblastomas and low grade gliomas. Different glioblastomas show a very heterogeneous expression of αvβ3 integrin, which ranges from slightly to very strong integrin expression similar to highly expressing non-CNS tumors. Subsequent analysis revealed that not only endothelial cells contribute to the overall amount of αvβ3 integrin in the tumors: In many malignant gliomas, about 85 percent of the overall integrin expression was derived from glial tumor cells.
Conclusions: The presented data lead to new insights in the pattern of αvβ3 integrin in gliomas. Since anti-angiogenic therapy with integrin αvβ3-antagonists has reached clinical trials for patients with malignant gliomas, minute detection and quantification of αvβ3 integrin expression could be a prerequisite for selection of patients suitable for this kind of additional therapy.