Hatina J, Kripnerová M, Tuková J, Šrámek J, Dvořák P, Pešta M, Dobrá J, Babuška V, Racek J, Sobol M, Philimonenko A, Hozák P, Czuba Z, Schulz W A, Strell C, Grimm S, Jennek S, Friedrich K-H
Institut für Biologie, Karlsuniversität Prag, Medizinische Fakultät zu Pilsen, Alej Svobody 76, 32300, Plzeň, Tschechische Republik,
Urologe A. 2015 Apr;54(4):516-25. doi: 10.1007/s00120-014-3754-3.
The histopathological structure of malignant tumours involves two essential compartments - the tumour parenchyma with the actual transformed cells, and the supportive tumour stroma. The latter consists of specialized mesenchymal cells, such as fibroblasts, macrophages, lymphocytes and vascular cells, as well as of their secreted products, including components of the extracellular matrix, matrix modifying enzymes and numerous regulatory growth factors and cytokines. In consequence, the tumour stroma has the ability to influence virtually all aspects of tumour development and progression, including therapeutic response.
In this article we review the current knowledge of tumor stroma interactions in urothelial carcinoma and present various experimental systems that are currently in use to unravel the biological basis of these heterotypic cell interactions.
For urothelial carcinoma, an extensive tumour stroma is quite typical and markers of activated fibroblasts correlate significantly with clinical parameters of advanced disease. Another clinically important variable is provided by the stromal expression of syndecan-1.
Integration of markers of activated stroma into clinical risk evaluation could aid to better stratification of urothelial bladder carcinoma patients. Elucidation of biological mechanisms underlying tumour-stroma interactions could provide new therapeutical targets.
恶性肿瘤的组织病理学结构包括两个基本部分——含有实际转化细胞的肿瘤实质，以及支持性肿瘤基质。后者由特殊的间充质细胞组成，如成纤维细胞、巨噬细胞、淋巴细胞和血管细胞，以及它们分泌的产物，包括细胞外基质成分、基质修饰酶和众多调节性生长因子及细胞因子。因此，肿瘤基质能够影响肿瘤发生发展的几乎所有方面，包括治疗反应。
在本文中，我们综述了目前关于尿路上皮癌中肿瘤基质相互作用的知识，并介绍了目前用于揭示这些异型细胞相互作用生物学基础的各种实验系统。
对于尿路上皮癌，广泛的肿瘤基质相当典型，活化成纤维细胞的标志物与晚期疾病的临床参数显著相关。基质中syndecan-1的表达提供了另一个重要的临床变量。
将活化基质的标志物整合到临床风险评估中有助于更好地对尿路上皮膀胱癌患者进行分层。阐明肿瘤-基质相互作用的生物学机制可为新的治疗靶点提供依据。
