Inhibition of tumor cell-induced platelet aggregation and experimental tumor metastasis by the synthetic Gly-Arg-Gly-Asp-Ser peptide.
Inhibition of tumor cell-induced platelet aggregation and experimental tumor metastasis by the synthetic Gly-Arg-Gly-Asp-Ser peptide.
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DOI：
10.1093/jnci/80.18.1461
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发表时间：
1988-11
期刊：
影响因子：
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通讯作者：
K. Ugen;M. Mahalingam;P. Klein;K. Kao
中科院分区：
文献类型：
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作者：
K. Ugen;M. Mahalingam;P. Klein;K. Kao
研究了鼠纤维肉瘤克隆 PAK 17.15 诱导血小板聚集 [肿瘤细胞诱导的血小板聚集 (TCIPA)] 的机制，因为该克隆的血小板激活对于肺部转移是必要的。 PAK 17.15 TCIPA 被 ADP 清除酶（例如腺苷三磷酸双磷酸酶或磷酸肌酸和肌酸磷酸激酶的混合物）完全抑制。 PAK 17.15 TCIPA 不涉及凝血酶和胶原蛋白。进一步的研究表明，ADP 很可能是由活化的血小板分泌的，而 PAK 17.15 细胞上的膜蛋白负责血小板的活化。由于 ADP 依赖性血小板聚集需要纤维蛋白原，并且可以被 Gly-Arg-Gly-Asp-Ser (GRGDS) 合成肽抑制，因此研究了该肽对 PAK 17.15 TCIPA 的影响。 PAK 17.15 TCIPA 被 GRGDS 肽 (0.4 mM) 完全抑制，但不受对照肽 Gly-Arg-Gly-Glu-Ser (0.8 mM) 的抑制。此外，GRGDS 肽抑制 PAK 17.15 细胞与固定化纤连蛋白的粘附。正如预期的那样，GRGDS 肽几乎完全抑制了 C57BL/6 小鼠静脉注射 PAK 17.15 细胞的肺部定植。我们的结果表明，GRGDS 可能通过干扰 TCIPA 以及肿瘤细胞与宿主细胞外基质成分的粘附来抑制肺转移。
The mechanism by which the murine fibrosarcoma clone PAK 17.15 induces platelet aggregation [tumor cell-induced platelet aggregation (TCIPA)] was studied because platelet activation by this clone is necessary for metastasis to the lungs. PAK 17.15 TCIPA was completely inhibited by ADP-clearing enzymes, such as apyrase, or a mixture of creatine phosphate and creatine phosphokinase. Thrombin and collagen were not involved in PAK 17.15 TCIPA. Further studies showed that ADP is most likely secreted from activated platelets and that membrane protein(s) on PAK 17.15 cells are responsible for platelet activation. Inasmuch as ADP-dependent platelet aggregation requires fibrinogen and can be inhibited by the Gly-Arg-Gly-Asp-Ser (GRGDS) synthetic peptide, the effect of this peptide on PAK 17.15 TCIPA was studied. PAK 17.15 TCIPA was completely inhibited by the GRGDS peptide (0.4 mM) but not by a control peptide, Gly-Arg-Gly-Glu-Ser (0.8 mM). In addition, the GRGDS peptide inhibited adhesion of PAK 17.15 cells to immobilized fibronectin. As expected, the GRGDS peptide almost completely inhibited lung colonization by iv injected PAK 17.15 cells in C57BL/6 mice. Our results indicate that GRGDS may inhibit pulmonary metastases by interfering with TCIPA as well as with tumor cell adhesion to extra-cellular matrix components in the host.