Rubina K A, Sysoeva V Yu, Zagorujko E I, Tsokolaeva Z I, Kurdina M I, Parfyonova Ye V, Tkachuk V A
Lomonosov Moscow State University, 31-5, Lomonosovsky av., Moscow, 119192, Russia.
Russian Cardiology Research Center, 3-rd Cherepkovskaya, 15a, Moscow, Moscow, 121552, Russia.
Arch Dermatol Res. 2017 Aug;309(6):433-442. doi: 10.1007/s00403-017-1738-z. Epub 2017 Apr 20.
There is substantial evidence implicating the urokinase system in tissue remodeling during neo-vascularization, inflammation, tumor invasion, and metastasis. Regulated degradation of the extracellular matrix at the leading edge of migrating cells, mediated by uPA and uPAR, is required for tissue remodeling, invasiveness, and angiogenesis. Psoriasis and basal cell carcinoma (BCC) are the most common skin diseases. Pathogenesis of both of them is associated with keratinocyte hyperproliferation, inflammatory cell migration, and angiogenesis-processes in which the plasminogen system (uPA, uPAR, tPA, and PAI-1) plays a crucial role. In the present study, the comparative analysis of uPA, uPAR, tPA, and PAI-1 expression in the normal skin, in the biopsies of patients with psoriasis vulgaris, and BCC was carried out. uPA, uPAR, and PAI-1 expression was up-regulated in the epidermis of psoriatic skin and in tumor cells in BCC. Increased uPAR expression was detected in the derma of psoriatic lesions and in the stroma surrounding tumor cells in BCC. Increased expression of uPA in epidermal cells in psoriasis and in tumor cells in BCC suggests an important role of the uPA system for aggressively proliferating and invading cells of epidermal origin. A possible activation of the stroma, as a result of uPA-uPAR interaction between tumor cells and the surrounding stroma, is suggested.
有大量证据表明,尿激酶系统在新生血管形成、炎症、肿瘤侵袭和转移过程中的组织重塑中发挥作用。由尿激酶型纤溶酶原激活物(uPA)和尿激酶型纤溶酶原激活物受体(uPAR)介导的迁移细胞前沿细胞外基质的有序降解,是组织重塑、侵袭和血管生成所必需的。银屑病和基底细胞癌(BCC)是最常见的皮肤疾病。它们的发病机制均与角质形成细胞过度增殖、炎症细胞迁移和血管生成有关,而纤溶酶原系统(uPA、uPAR、组织型纤溶酶原激活物(tPA)和纤溶酶原激活物抑制剂-1(PAI-1))在这些过程中起着关键作用。在本研究中,对正常皮肤、寻常型银屑病患者活检组织和基底细胞癌中uPA、uPAR、tPA和PAI-1的表达进行了比较分析。uPA、uPAR和PAI-1的表达在银屑病皮肤的表皮和基底细胞癌的肿瘤细胞中上调。在银屑病皮损的真皮和基底细胞癌肿瘤细胞周围的基质中检测到uPAR表达增加。银屑病表皮细胞和基底细胞癌肿瘤细胞中uPA表达增加,提示uPA系统对表皮来源的侵袭性增殖和侵袭细胞具有重要作用。提示肿瘤细胞与周围基质之间的uPA-uPAR相互作用可能导致基质激活。