Molecular identification of Aggrus/T1α as a platelet aggregation-inducing factor expressed in colorectal tumors
Molecular identification of Aggrus/T1α as a platelet aggregation-inducing factor expressed in colorectal tumors
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DOI：
10.1074/jbc.m309935200
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发表时间：
2003-12-19
影响因子：
4.8
通讯作者：
Tsuruo, T
中科院分区：
文献类型：
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作者：
Kato, Y;Fujita, N;Tsuruo, T
血小板在止血、血栓形成和抗微生物宿主防御中起重要作用，并且还参与炎症、组织修复和肿瘤转移的诱导。我们以前的特点是血小板聚集诱导唾液酸糖蛋白（Aggrus/gp 44）过表达的肿瘤细胞表面。由于能够特异性识别Aggrus的血小板聚集中和单克隆抗体8 F11抑制肿瘤诱导的血小板聚集，我们先前通过8 F11亲和层析纯化了Aggrus，发现纯化的Aggrus具有诱导血小板聚集的能力。在这里，我们表明Aggrus是相同的T1 α/gp 38 P/ OTS-8抗原，其在肿瘤中的功能是未知的。小鼠聚集蛋白及其人类同源物（也称为T1 α-2/gp36）的表达诱导血小板聚集，而不需要血浆成分。使用8 F11抗体，我们确定了高度保守的血小板聚集刺激结构域与推定的O-糖基化苏氨酸残基作为表现出血小板聚集诱导能力的关键决定因素。我们比较了人聚集蛋白mRNA的表达水平，使用含有160个cDNA对样品的阵列，这些样品来自多个人致瘤组织和相应的正常组织，来自个体患者。我们发现大多数结直肠肿瘤患者中aggrus的表达水平增强。为了证实蛋白质表达，我们产生了抗人聚集蛋白多克隆抗体。免疫组化分析显示，Aggrus表达频繁上调，在结直肠肿瘤。这些结果表明，Aggrus/T1 α是一个新发现的，血小板聚集诱导因子在结直肠肿瘤中表达。
Platelets play an important role in hemostasis, thrombosis, and antimicrobial host defense and are also involved in the induction of inflammation, tissue repair, and tumor metastasis. We have previously characterized the platelet aggregation-inducing sialoglycoprotein (Aggrus/gp44) overexpressed on the surface of tumor cells. Because a platelet aggregation-neutralizing 8F11 monoclonal antibody that could specifically recognize Aggrus suppressed tumor-induced platelet aggregation, we have previously purified Aggrus by 8F11-affinity chromatography and found that purified Aggrus possessed the ability to induce aggregation of platelets. Here we show that Aggrus is identical to the T1alpha/gp38P/ OTS-8 antigen, the function of which in tumors is unknown. Expression of mouse Aggrus and its human homologue (also known as T1alpha-2/gp36) induced platelet aggregation without requiring plasma components. Using the 8F11 antibody, we identified the highly conserved platelet aggregation-stimulating domain with putative O-glycosylated threonine residues as the critical determinant for exhibiting platelet aggregation-inducing capabilities. We compared the expression level of human aggrus mRNA using an array containing 160 cDNA pair samples derived from multiple human tumorigenic and corresponding normal tissues from individual patients. We found that expression level of aggrus was enhanced in most colorectal tumor patients. To confirm the protein expression, we generated anti-human Aggrus polyclonal antibodies. Immunohistochemical analysis revealed that Aggrus expression was frequently up-regulated in colorectal tumors. These results suggest that Aggrus/T1alpha is a newly identified, platelet aggregation-inducing factor expressed in colorectal tumors.