Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression
Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression
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DOI：
10.1007/s00401-006-0063-y
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发表时间：
2006-05-01
影响因子：
12.7
通讯作者：
Matsutani, M
中科院分区：
文献类型：
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作者：
Mishima, K;Kato, Y;Matsutani, M
Podoplanin（aggrus）是一种在淋巴管内皮细胞上表达的粘蛋白样跨膜唾液酸糖蛋白。Podoplanin参与癌细胞迁移、侵袭、转移和恶性进展，并且可能参与血小板聚集。以前，我们发现podoplanin在中枢神经系统（CNS）生殖细胞瘤中表达上调，但在非生殖细胞瘤性生殖细胞肿瘤中没有，除了少数未成熟畸胎瘤的部分。然而，关于它在中枢神经系统星形细胞肿瘤中的作用的信息很少。在这项研究中，188星形细胞肿瘤（30弥漫性星形细胞瘤，43间变性星形细胞瘤，和115胶质母细胞瘤）进行了研究，使用免疫组织化学与抗podoplanin抗体，YM-1。在43例间变性星形细胞瘤中有11例（25.6%）和115例胶质母细胞瘤中有54例（47.0%）podoplanin表达于间变性星形细胞瘤细胞和胶质母细胞瘤细胞的表面，尤其是坏死区和增殖的内皮细胞周围。然而，周围脑实质未被YM-1染色。另一方面，在弥漫性星形细胞瘤中未观察到podoplanin表达（0/30：0%）。此外，我们研究了podoplanin的表达，采用定量实时PCR和Western印迹分析在54冷冻星形细胞肿瘤（6弥漫性星形细胞瘤，14间变性星形细胞瘤，和34胶质母细胞瘤）。Podoplanin mRNA和蛋白在胶质母细胞瘤中的表达明显高于间变性星形细胞瘤。这些数据表明podoplanin表达可能与星形细胞肿瘤的恶性程度有关。
Podoplanin (aggrus) is a mucin-like transmembrane sialoglycoprotein that is expressed on lymphatic endothelial cells. Podoplanin is putatively involved in cancer cell migration, invasion, metastasis, and malignant progression and may be involved in platelet aggregation. Previously, we showed upregulated expression of podoplanin in central nervous system (CNS) germinomas, but not in non-germinomatous germ cell tumors, except for parts of immature teratomas in limited numbers. However, little information exists about its role in CNS astrocytic tumors. In this study, 188 astrocytic tumors (30 diffuse astrocytomas, 43 anaplastic astrocytomas, and 115 glioblastomas) were investigated using immunohistochemistry with an anti-podoplanin antibody, YM-1. In 11 of 43 anaplastic astrocytomas (25.6%) and in 54 of 115 glioblastomas (47.0%), podoplanin was expressed on the surface of anaplastic astrocytoma cells and glioblastoma cells, especially around necrotic areas and proliferating endothelial cells. However, the surrounding brain parenchyma was not stained by YM-1. On the other hand, podoplanin expression was not observed in diffuse astrocytoma (0/30: 0%). Furthermore, we investigated the expression of podoplanin using quantitative real-time PCR and Western blot analysis in 54 frozen astrocytic tumors (6 diffuse astrocytomas, 14 anaplastic astrocytomas, and 34 glioblastomas). Podoplanin mRNA and protein expression were markedly higher in glioblastomas than in anaplastic astrocytomas. These data suggest that podoplanin expression might be associated with malignancy of astrocytic tumors.