Milsom Chloe, Rak Janusz
Henderson Research Centre, McMaster University, Hamilton, Ont., Canada.
Pathophysiol Haemost Thromb. 2008;36(3-4):160-76. doi: 10.1159/000175154. Epub 2009 Jan 27.
Tissue factor (TF), the key regulator of haemostasis and angiogenesis, is also involved in the pathology of several diseases, including cardiovascular, inflammatory and neoplastic conditions. In the latter, TF is upregulated by cancer cells, as well as by certain host cells, and it is the interactions between these distinct pools of TF-expressing cells that likely influence tumour progression in several ways. Furthermore, the release of TF microparticles into the circulation is thought to contribute to the systemic coagulopathies commonly observed in cancer patients. The direct regulation of TF by oncogenic events has provided a plausible explanation for the relatively common overexpression of TF in various cancers and its involvement in tumour growth, angiogenesis, metastasis and coagulopathy. However, this constitutive influence is modified by the tumour microenvironment, cellular interactions and host factors rendering TF expression patterns complex and heterogeneous. It appears that in many biological contexts TF plays a central role in disease progression and thereby potentially constitutes an attractive therapeutic target, especially in scenarios where the risk of bleeding can be avoided by selecting appropriate medications, refined dosing or by targeting the signalling component of TF activity. The efficacy and safety of such approaches still awaits clinical verification.
组织因子（TF）是止血和血管生成的关键调节因子，也参与多种疾病的病理过程，包括心血管疾病、炎症性疾病和肿瘤性疾病。在肿瘤性疾病中，TF由癌细胞以及某些宿主细胞上调表达，正是这些表达TF的不同细胞池之间的相互作用可能以多种方式影响肿瘤进展。此外，TF微粒释放到循环系统中被认为是导致癌症患者常见的全身性凝血病的原因之一。致癌事件对TF的直接调控为TF在各种癌症中相对常见的过表达及其参与肿瘤生长、血管生成、转移和凝血病提供了一个合理的解释。然而，这种组成性影响会受到肿瘤微环境、细胞相互作用和宿主因素的修饰，使得TF的表达模式复杂且具有异质性。在许多生物学背景下，TF似乎在疾病进展中起着核心作用，因此可能构成一个有吸引力的治疗靶点，特别是在通过选择合适的药物、精确给药或靶向TF活性的信号传导成分可以避免出血风险的情况下。这些方法的疗效和安全性仍有待临床验证。
