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组织因子启动的凝血酶生成激活恶性黑色素瘤细胞上的信号凝血酶受体。

Tissue factor-initiated thrombin generation activates the signaling thrombin receptor on malignant melanoma cells.

作者信息

Fischer E G, Ruf W, Mueller B M

机构信息

Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Cancer Res. 1995 Apr 15;55(8):1629-32.

PMID:7712465
Abstract

The human melanoma cell line M24met expresses tissue factor, the cellular initiator of the blood coagulation cascade. Blocking of the coagulation pathways at the level of tissue factor, factor Xa, or thrombin inhibits hematogenous M24met metastasis in SCID mice, implicating a role for thrombin generation in this process. Dependent on cell surface tissue factor activity, M24met cells generate thrombin in vitro. Thrombin and the thrombin receptor agonist peptide TRP-14 activate a signaling pathway in M24met cells that involves an increase in intracellular calcium and induces cell proliferation. Immunofluorescence evidences expression of the signaling thrombin receptor on these cells. Thus, M24met melanoma cells express both the initiating cell surface receptor for the coagulation pathways and the central signaling receptor of the coagulation system, suggesting the in situ generation of proliferative signals which can contribute to the malignant phenotype.

摘要

人黑色素瘤细胞系M24met表达组织因子,即血液凝固级联反应的细胞启动因子。在组织因子、凝血因子Xa或凝血酶水平阻断凝血途径可抑制M24met在SCID小鼠中的血行转移,这表明凝血酶生成在此过程中发挥作用。依赖于细胞表面组织因子活性,M24met细胞在体外生成凝血酶。凝血酶和凝血酶受体激动肽TRP-14激活M24met细胞中的一条信号通路,该通路涉及细胞内钙增加并诱导细胞增殖。免疫荧光证实这些细胞上存在信号传导凝血酶受体的表达。因此,M24met黑色素瘤细胞既表达凝血途径的起始细胞表面受体,也表达凝血系统的中心信号受体,这表明原位生成的增殖信号可能促成恶性表型。

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