Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain
Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain
复制标题
DOI：
10.1016/j.bbrc.2006.08.171
复制
发表时间：
2006-11-03
影响因子：
3.1
通讯作者：
Osawa, Motoki
中科院分区：
文献类型：
--
作者：
Kato, Yukinari;Kaneko, Mika Kato;Osawa, Motoki
粘蛋白型唾液酸糖蛋白，podoplanin（aggrus），是癌细胞上的血小板聚集因子。我们先前描述了podoplanin在恶性星形细胞肿瘤包括胶质母细胞瘤中的表达上调。其表达与肿瘤恶性程度有关。在本研究中，我们调查podoplanin表达和血小板聚集活性的胶质母细胞瘤细胞系。首先，我们建立了一个高反应性的抗podoplanin抗体，NZ-1，它可以完全抑制podoplanin诱导的血小板聚集。在15个胶质母细胞瘤细胞系中，LN 319高表达podoplanin并诱导血小板聚集。使用凝集素微阵列的聚糖分析显示，LN 319上的podoplanin具有唾液酸，这在podoplanin诱导的血小板聚集中是重要的。有趣的是，NZ-1中和了LN 319引起的血小板聚集。这些结果表明podoplanin是LN 319诱导血小板聚集的主要原因。我们推断，NZ-1是有用的，以确定血小板聚集是否是podoplanin特异性或没有。此外，podoplanin可能成为胶质母细胞瘤抗体治疗的一个靶点。(c)2006年爱思唯尔公司All rights reserved.
The mucin-type sialoglycoprotein, podoplanin (aggrus), is a platelet-aggregating factor on cancer cells. We previously described up-regulated expression of podoplanin in malignant astrocytic tumors including glioblastoma. Its expression was associated with tumor malignancy. In the present study, we investigated podoplanin expression and platelet-aggregating activities of glioblastoma cell lines. First, we established a highly reactive anti-podoplanin antibody, NZ-1, which inhibits podoplanin-induced platelet aggregation completely. Of 15 glioblastoma cell lines, LN319 highly expressed podoplanin and induced platelet aggregation. Glycan profiling using a lectin microarray showed that podoplanin on LN319 possesses sialic acid, which is important in podoplanin-induced platelet aggregation. Interestingly, NZ-1 neutralized platelet aggregation by LN319. These results suggest that podoplanin is a main reason for platelet aggregation induced by LN319. We infer that NZ-1 is useful to determine whether platelet aggregation is podoplanin-specific or not. Furthermore, podoplanin might become a therapeutic target of glioblastoma for antibody-based therapy. (c) 2006 Elsevier Inc. All rights reserved.