Departamento de Medicina Interna y Centro de Cáncer, The American British Cowdray Medical Center.
Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez.
Tohoku J Exp Med. 2020 Feb;250(2):121-128. doi: 10.1620/tjem.250.121.
The fibrinolytic system plays an important role in breast cancer, favoring progression through extracellular-matrix degradation, angiogenesis, apoptosis and cellular proliferation. The expression of urokinase-type plasminogen activator (uPA) in breast cancer tissue is widely recognized as an unfavorable prognostic factor. However, fibrinolytic activity associated with uPA cannot be reliably measured in the blood because of the rapid inhibition of uPA by plasminogen activator inhibitor-1 (PAI-1). By contrast, circulating microvesicles (Mvs) in peripheral blood protect bound enzymes from inhibition. Mvs are extracellular vesicles, released from various types of cells, and their size fluctuates between 100 and 1,000 nm. Mvs carry DNA, RNA, miRNA, and proteins, thereby serving as a source of horizontal communication between cells. We investigated whether fibrinolytic activity on circulating Mvs reflects breast cancer progression. The study population consisted of 13 patients with breast cancer and 13 healthy women. The cancer patients included 4 patients in remission, 3 patients with locally advanced cancer, and 6 with metastatic disease. Mvs were isolated from peripheral blood, quantified by a protein concentration method, and their fibrinolytic potential was measured by their capacity to generate plasmin. Although the quantity of Mvs found in patients with cancer and healthy individuals was similar, plasmin generated on Mvs was twice the amount in patients with metastasis than in healthy women (P < 0.05), underlying the value of this distinctive parameter. The data suggest that in breast cancer patients, higher fibrinolytic activity of circulating Mvs could be related to progression and metastasis of breast cancer.
纤溶系统在乳腺癌中起着重要作用，通过细胞外基质降解、血管生成、细胞凋亡和细胞增殖促进肿瘤进展。组织中尿激酶型纤溶酶原激活物(uPA)的表达被广泛认为是预后不良的因素。然而，由于纤溶酶原激活物抑制剂-1(PAI-1)对 uPA 的快速抑制，uPA 相关的纤溶活性在血液中无法可靠测量。相比之下，外周血中的循环微泡(Mv)可以保护结合的酶免受抑制。Mv 是由各种类型的细胞释放的细胞外囊泡，其大小在 100 到 1000nm 之间波动。Mv 携带 DNA、RNA、miRNA 和蛋白质，从而成为细胞间水平通讯的来源。我们研究了循环 Mv 上的纤溶活性是否反映了乳腺癌的进展。研究人群包括 13 名乳腺癌患者和 13 名健康女性。癌症患者包括 4 名缓解期患者、3 名局部晚期癌症患者和 6 名转移性疾病患者。Mv 从外周血中分离出来，用蛋白质浓度法进行定量，并通过生成纤溶酶的能力来测量其纤溶潜能。尽管癌症患者和健康个体中发现的 Mv 数量相似，但转移性癌症患者的 Mv 生成的纤溶酶是健康女性的两倍(P < 0.05)，这突显了这一独特参数的价值。数据表明，在乳腺癌患者中，循环 Mv 的纤溶活性升高可能与乳腺癌的进展和转移有关。
