糖胺聚糖和激活的接触系统在癌症患者血浆中的变化。

Glycosaminoglycans and activated contact system in cancer patient plasmas.

机构信息

Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO, USA.

出版信息

Prog Mol Biol Transl Sci. 2010;93:473-95. doi: 10.1016/S1877-1173(10)93020-2.

Abstract

Oncogenic mutations create cancer cells. Cancer cells require thrombin for growth, angiogenesis, and metastasis. All cancer patients display a hypercoagulable state, which includes platelet activation, blood coagulation, complement activation, vasodilatation, and inflammation. This often results in thrombosis, the second leading cause of death in cancer patients. It is established that chemically oversulfated glycosaminoglycans (GAGs) induce thrombin generation through contact system activation in human plasma. Thrombin is responsible for thrombosis. In this chapter, we show that plasmas from lung cancer patients contain activated contact systems apparent by the absence of high molecular weight kininogen and processed C1inh, by abnormal kallikrein and thrombin activities, and by increased glucosamine, galactosamine, and GAG levels. Activated contact systems were also evident in plasmas from breast, colon, and pancreatic cancer patients. These data suggest that GAGs or other molecules produced by tumors induce abnormal thrombin generation through contact system activation. Therefore, the contact system and glycans represent new targets for cancer diagnosis, prevention, and treatment.

摘要

致癌突变创造癌细胞。癌细胞的生长、血管生成和转移都需要凝血酶。所有癌症患者都表现出高凝状态,包括血小板激活、血液凝固、补体激活、血管舒张和炎症。这通常会导致血栓形成,是癌症患者的第二大致死原因。现已证实,化学过度硫酸化糖胺聚糖(GAG)通过人血浆中的接触系统激活诱导凝血酶生成。凝血酶可导致血栓形成。在本章中,我们展示了来自肺癌患者的血浆中存在激活的接触系统,这表现在高分子量激肽原和加工后的 C1inh 缺失、异常激肽和凝血酶活性以及葡萄糖胺、半乳糖胺和 GAG 水平升高。乳腺癌、结肠癌和胰腺癌患者的血浆中也存在激活的接触系统。这些数据表明,肿瘤产生的 GAG 或其他分子通过接触系统激活诱导异常凝血酶生成。因此,接触系统和聚糖代表了癌症诊断、预防和治疗的新靶点。

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