Artikel
Expression of lymphangiogenesis-related factors in glioblastomas – a novel aspect in glioma angiogenesis
Expression des Lymphangiogenese-assoziierter Faktoren in Glioblastomen – neue Aspekte der Angiogenese in Gliomen
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Autoren
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S. Grau
- Neurochirurgische Klinik Klinikum Großhadern, LMU München
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F. Trillsch
- Neurochirurgische Klinik Klinikum Großhadern, LMU München
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N. Thon
- Neurochirurgische Klinik Klinikum Großhadern, LMU München
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J.-C. Tonn
- Neurochirurgische Klinik Klinikum Großhadern, LMU München
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P. Nelson
- Medizinische Klinik Innenstadt, LMU München
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R. Goldbrunner
- Neurochirurgische Klinik Klinikum Großhadern, LMU München
| Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: Malignant gliomas are highly vascularized tumors. The vascular endothelial growth factor receptor-2 (VEGFR2) system has been established as a key regulator for glioma neoangiogenesis. VEGFR3 is indispensable in embryonic vasculogenesis and its later expression usually restricted to lymphatic endothelium. However, there is growing evidence for a role of VEGFR3 in tumor malignancy and metastasis. Presence and role of VEGFR3, its ligands VEGF-C and -D as well as lymphatic markers like podoplanin has not been investigated in malignant gliomas up to date. Here we report the expression of these receptors and markers in human gliomas depending on tumor malignancy.
Methods: Samples of human glioblastoma (n=18), low grade astrocytoma (n=6) and non neoplastic brain (n=3) were investigated for expression of VEGFR3, VEGF-C and VEGF-D on mRNA and protein level by use of real time PCR, immunohistochemistry and Western blot analysis.
Results: In immunohistochemistry 18/18 glioblastomas showed a high expression of VEGFR3, VEGF-C and VEGF-D. VEGFR3 was mainly present on tumor-vessel endothelium, however, in areas of high vessel density also numerous stromal cells stained positive. VEGF-C and -D was expressed strongest in areas of high vessel density. In low grade astrocytomas, VEGFR3 was positive in single endothelial cells of some larger vessels in 2/6 samples while being absent in normal brain. Podoplanin was detected in all glioblastomas. On mRNA level, transcripts for VEGFR3 and podoplanin were significantly elevated in 6/6 glioblastomas compared to low grade astrocytomas and normal brain (p<0.01). Western blot analysis showed a high amount of VEGF-C and -D as well as VEGFR3 in 6/6 glioblastomas while being absent in normal brain and low grade tumors.
Conclusions: The presence of VEGFR3 as well as its ligands VEGF-C and -D indicates the presence of an additional angiogenic signaling system. This may lead to a more profound understanding of tumor angiogenesis and glioma progression. Moreover, this data might influence future concepts of antiangiogenic therapy.
