Graeff H, Jänicke F, Schmitt M
Frauenklinik, Technischen Universität München.
Geburtshilfe Frauenheilkd. 1991 Feb;51(2):90-9. doi: 10.1055/s-2007-1023682.
The capacity of solid tumours to invade the surrounding tissue and to metastasize, is correlated with the formation and degradation of structural elements in the vicinity of the tumour cells. Substances with both procoagulant activity and fibrinolytic activity are important factors in the formation or degradation of a "fibrin-fibronectin-gel matrix". This gel is subsequently transformed into the extracellular matrix, which, together with cells, will form the tumour stroma. When analyzing tumour stroma degradation products, it is obvious that the protease plasmin catalyses the disintegration of fibrin and fibronectin. Additional compounds of the tumour stroma and of the basal membrane are also, at least in part, broken down by plasmin or other proteases, such as collagenase IV and cathepsin D. The plasminogen activator urokinase (uPA) seems to play a central role as it was shown that elevated content of uPA is correlated with a high risk of early relapse and shorter overall survival, at least in breast cancer. It has been shown, that by means of quantifying uPA, patients with a relative high or low risk can even be selected within the classical risk groups, which so far are defined by the locoregional extension of the tumour and the hormone receptor status only. Evidently, as uPA content in human breast cancer tissue is an independent prognostic factor, one may speculate, that those experimental or in vitro data, which correlated increase in uPA-synthesis with malignancy, may be of direct relevance for human tumour biology. Moreover, due to these recent observations on the prognostic significance of tumour-associated proteases, new aspects for the selection of risk collectives within the node-negative breast cancer patients for adjuvant therapy have to be considered. It may well be possible, that one may affect tumour invasion and metastasis by inhibiting protease action of solid tumours by disturbing the binding of proteases to tumour cell surface receptors. As it is only a quantitative aspect, which separates benign physiological processes from tumour cell pathophysiology, experimental evidence suggests, that less drastic forms of palliative therapy can be proposed.
实体瘤侵袭周围组织并发生转移的能力，与肿瘤细胞附近结构成分的形成和降解相关。具有促凝血活性和纤维蛋白溶解活性的物质是“纤维蛋白-纤连蛋白-凝胶基质”形成或降解的重要因素。这种凝胶随后转化为细胞外基质，细胞外基质与细胞一起形成肿瘤基质。在分析肿瘤基质降解产物时，很明显蛋白酶纤溶酶催化纤维蛋白和纤连蛋白的分解。肿瘤基质和基底膜的其他成分也至少部分地被纤溶酶或其他蛋白酶分解，如IV型胶原酶和组织蛋白酶D。纤溶酶原激活物尿激酶（uPA）似乎起着核心作用，因为已表明uPA含量升高与早期复发风险高和总生存期短相关，至少在乳腺癌中是如此。已经表明，通过定量uPA，甚至可以在经典风险组内选择相对高风险或低风险的患者，到目前为止，经典风险组仅由肿瘤的局部区域扩展和激素受体状态定义。显然，由于人乳腺癌组织中的uPA含量是一个独立的预后因素，人们可能会推测，那些将uPA合成增加与恶性肿瘤相关联的实验或体外数据，可能与人类肿瘤生物学直接相关。此外，由于最近关于肿瘤相关蛋白酶预后意义的这些观察结果，必须考虑在淋巴结阴性乳腺癌患者中选择风险群体进行辅助治疗的新方面。很有可能通过干扰蛋白酶与肿瘤细胞表面受体的结合来抑制实体瘤的蛋白酶作用，从而影响肿瘤的侵袭和转移。由于将良性生理过程与肿瘤细胞病理生理学区分开来的只是一个定量方面，实验证据表明，可以提出不太激进的姑息治疗形式。
