Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Thromb Res. 2012 Apr;129 Suppl 1:S80-4. doi: 10.1016/S0049-3848(12)70022-1.
Cancer is frequently associated with activation of blood coagulation, which in turn has been suggested to promote tumor growth and metastasis. Indeed, low molecular weight heparin treatment significantly prolongs the survival of a wide variety of patients with cancer. Based on this notion that anticoagulant treatment seems to benefit cancer patients, recent experiments aimed to elucidate the importance of the natural anticoagulant protein C pathways in cancer progression. Interestingly, these experiments showed that the repeated administration of exogenous activated protein C limits cancer cell extravasation in experimental animal models. In line, reducing endogenous activated protein C activity dramatically increased the number of experimental metastasis. These data thus strongly suggest that exogenous activated protein C administration may be a novel therapeutic avenue to limit cancer metastasis thereby prolonging overall survival of cancer patients. The current review provides an overview of recent data on the role of the protein C pathway in cancer metastasis. It discusses the potential of activated protein C as a novel target to reduce cancer progression, it points to several limitations of activated protein C administration in the setting of cancer cell metastasis and it suggest zymogen protein C as an attractive alternative.
癌症常与血液凝固的激活有关，而血液凝固的激活又被认为可促进肿瘤生长和转移。事实上，低分子量肝素治疗显著延长了各种癌症患者的生存期。基于抗凝治疗似乎对癌症患者有益的这一观点，最近的实验旨在阐明天然抗凝蛋白 C 途径在癌症进展中的重要性。有趣的是，这些实验表明，外源性激活蛋白 C 的重复给药可限制实验动物模型中的癌细胞外渗。与此一致的是，降低内源性激活蛋白 C 活性会显著增加实验性转移的数量。因此，这些数据强烈表明，外源性激活蛋白 C 给药可能是一种限制癌症转移、延长癌症患者总生存期的新的治疗途径。本综述概述了蛋白 C 途径在癌症转移中的作用的最新数据。它讨论了激活蛋白 C 作为降低癌症进展的新靶点的潜力，指出了在癌细胞转移背景下给予激活蛋白 C 存在的几个局限性，并提出了酶原蛋白 C 作为一种有吸引力的替代物。
