Rudroff C, Schafberg H, Nowak G, Weinel R, Scheele J, Kaufmann R
Department of Surgery, Friedrich Schiller University Jena, Germany.
Pancreas. 1998 Mar;16(2):189-94. doi: 10.1097/00006676-199803000-00013.
In this article, the "tethered ligand" thrombin receptor was identified on human pancreatic tumor cells, MIA PaCa-2, using immunofluorescence studies with a monoclonal anti-thrombin receptor antibody. Pharmacological characterization, using 3H-labeled thrombin receptor activating peptide-6 (TRAP-6) as radioligand, demonstrated a single class of high-affinity binding sites (KD = 9.1+/-1.8 x 10(-7) M) and a binding capacity of 13.9+/-0.7 fmol/mg protein. These binding sites represent functional thrombin receptors, as shown by alpha-thrombin- and TRAP-6-induced mobilization of free intracellular calcium, protein kinase C translocation from cytosol to the cell membrane, and stimulation of DNA synthesis in MIA PaCa-2 cells. These results provide the first identification of tethered ligand thrombin receptor in human pancreatic cancer cells and suggest thrombin receptor involvement in mechanisms of human pancreatic tumor progression.
在本文中，利用单克隆抗凝血酶受体抗体进行免疫荧光研究，在人胰腺肿瘤细胞MIA PaCa-2上鉴定出“拴系配体”凝血酶受体。使用3H标记的凝血酶受体激活肽-6（TRAP-6）作为放射性配体进行药理学特性分析，结果显示存在一类单一的高亲和力结合位点（KD = 9.1±1.8×10⁻⁷ M），结合容量为13.9±0.7 fmol/mg蛋白质。这些结合位点代表功能性凝血酶受体，α-凝血酶和TRAP-6诱导的细胞内游离钙动员、蛋白激酶C从胞质溶胶向细胞膜的转位以及MIA PaCa-2细胞中DNA合成的刺激均证明了这一点。这些结果首次在人胰腺癌细胞中鉴定出拴系配体凝血酶受体，并提示凝血酶受体参与人胰腺肿瘤进展机制。
