Contrino J, Hair G, Kreutzer D L, Rickles F R
Department of Medicine, University of Connecticut School of Medicine 06032, USA.
Nat Med. 1996 Feb;2(2):209-15. doi: 10.1038/nm0296-209.
Expression of tissue factor (TF) in the endothelium has been observed only rarely in human disease and has been thought to be elaborated on the surface of vascular endothelial cells (VECs) in vitro as an artifact of tissue culture. Using monoclonal antibodies and a novel probe for functional TF, we have localized TF to the VECs (and tumor cells) within the tumors of seven patients with invasive breast cancer but not in the VECs (or tumor cells) of benign tumors from ten patients with fibrocystic disease of the breast. The potent procoagulant TF was shown to be a marker of the initiation of angiogenesis in human breast cancer. Further evidence that the TF was the demonstration of a similar distribution of cross-linked fibrin only in the VECs of the malignant tumors. We interpret these data as further support for the concept that tumor cells can activate nearby VECs and regulate blood vessel growth in vivo. Large clinical pathologic studies will be necessary to determine whether TF is a useful marker for the "switch" to the angiogenic phenotype" in human breast disease and/or correlates with the thromboembolic complications of breast cancer.
组织因子(TF)在内皮中的表达在人类疾病中仅很少被观察到,并且在体外被认为是在血管内皮细胞(VEC)表面形成的一种组织培养假象。使用针对功能性TF的单克隆抗体和一种新型探针,我们将TF定位到7例浸润性乳腺癌患者肿瘤内的VEC(和肿瘤细胞)中,但在10例乳腺纤维囊性疾病患者的良性肿瘤的VEC(或肿瘤细胞)中未发现。强效促凝TF被证明是人类乳腺癌血管生成起始的一个标志物。进一步的证据是,仅在恶性肿瘤的VEC中显示出交联纤维蛋白的类似分布。我们将这些数据解释为对肿瘤细胞可激活附近VEC并在体内调节血管生长这一概念的进一步支持。需要进行大规模临床病理研究来确定TF是否是人类乳腺疾病中向血管生成表型“转变”的有用标志物和/或与乳腺癌的血栓栓塞并发症相关。