Artikel
Expression of lymphangiogenesis-related factors in malignant gliomas
Expression lymphangiogener Faktoren in malignen Gliomen
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Veröffentlicht: | 11. April 2007 |
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Gliederung
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Objective: Tumour induced angiogenesis is a key feature of malignant gliomas representing a novel target for neoadjuvant therapies. Glioma vessels are characterized by irregular shape, glomerulum-like formations and widespread thrombosis. Besides receptors and mechansims well known from hemangiogenesis we investigated the presence and origin of several lymphatic markers such as VEGFR3, VEGF-C, VEGF-D, podoplanin, prox-1 and LYVE-1.
Methods: Expression of VEGFR3, VEGF-C and –D, podoplanin, Prox-1, and Lyve-1 was investigated in human gliomas of different grade (n: GBM=18, WHO°III=10, WHO°II=6) and non neoplastic brain (n=3) on protein level by immunohistochemistry and Western Blotting, mRNA level was measured by real-time PCR. Epitope carrying cells were isolated from tumor tissue and further characterized by FACS and immunofluorescence.
Results: Lymphatic markers VEGFR3, podoplanin and Prox-1 are strongly expressed in all malignant gliomas investigated (WHO°III and IV). VEGFR3 was almost entirely located on tumor endothelium, while podoplanin was localised in perivascular tissue in WHO° IV tumors but expressed also on tumor endothelium in WHO°III. Low grade tumors WHO°II showed little to no expression. Non neoplastic brain was negative for all antigens investigated. VEGFR3+ cells showed expression of typical endothelial markers, while podoplanin+ cells showed a complex antigen pattern including CD14 and CD146.
Conclusions: Lymphatic factors are highly expressed in malignant gliomas (WHO°III and IV) while being absent in low grade tumors. This links to a grade dependent expression of these factors promising new insights into the angiogenic switch during glioma progression.