Klinik für Urologie und Kinderurologie, Zentrum der Chirurgie, Johann Wolfgang Goethe-Universitätsklinik, Frankfurt am Main, Germany.
World J Urol. 2010 Aug;28(4):465-71. doi: 10.1007/s00345-010-0539-1. Epub 2010 Mar 25.
Maspin belongs to the serpin family and has been shown to suppress tumor growth and metastasis in several tumor types. The role of maspin in bladder carcinoma has not been fully elucidated, and the object of this study was to investigate whether maspin contributes to bladder tumor adhesion to vascular endothelial cells (HUVEC).
Expression of maspin-coding mRNA was evaluated in a panel of bladder carcinoma cell lines. Maspin distribution in maspin mRNA(high) versus maspin mRNA(low) cells was further analyzed by flow cytometry and confocal microscopy. Adhesion to HUVEC was measured in a coculture model and correlated with the surface-bound maspin.
Maspin(high) (RT-4, RT-112) cell lines strongly attached to HUVEC, whereas maspin(low) (UMUC-3, MGH-U1) cell lines poorly adhered to HUVEC. Distinct cytoplasmic maspin accumulation and moderate surface-bound maspin was found in RT-4 cells. Blocking maspin surface receptors prevented tumor cell attachment to HUVEC, indicating that surface-bound maspin is responsible for triggering cell adhesion. PMA-triggered elevation of surface-bound maspin was accompanied by an enhanced adhesion capacity of RT-4 cells, compared to controls. Finally, exposing the bladder carcinoma cells to the differentiation-inducing agent valproic acid led to a surface-bound (but not cytoplasmic) maspin decrease, paralleled by a significant reduction in tumor cell binding to HUVEC.
Surface-bound maspin directly controls bladder carcinoma cell adhesion to the vascular wall. Blocking this process may prevent transendothelial migration and tumor cell dissemination. Therefore, therapeutic down-regulation of surface-bound maspin might become an option to prevent tumor spread into distant organs.
Maspin 属于丝氨酸蛋白酶抑制剂家族，已被证实能抑制多种肿瘤类型的肿瘤生长和转移。Maspin 在膀胱癌中的作用尚未完全阐明，本研究旨在探讨 Maspin 是否有助于膀胱癌黏附于血管内皮细胞（HUVEC）。
在一系列膀胱癌细胞系中评估了 maspin 编码 mRNA 的表达。通过流式细胞术和共聚焦显微镜进一步分析了 maspin mRNA（高）与 maspin mRNA（低）细胞中 Maspin 的分布。在共培养模型中测量了黏附作用，并与表面结合的 Maspin 相关联。
Maspin（高）（RT-4、RT-112）细胞系强烈黏附于 HUVEC，而 Maspin（低）（UMUC-3、MGH-U1）细胞系则很少黏附于 HUVEC。在 RT-4 细胞中发现了明显的细胞质 Maspin 积累和中等表面结合的 Maspin。阻断 Maspin 表面受体可防止肿瘤细胞黏附于 HUVEC，表明表面结合的 Maspin 是触发细胞黏附的原因。与对照组相比，PMA 触发的表面结合 Maspin 升高伴随着 RT-4 细胞黏附能力的增强。最后，将膀胱癌细胞暴露于诱导分化剂丙戊酸可导致表面结合（而非细胞质）Maspin 减少，同时肿瘤细胞与 HUVEC 的结合显著减少。
表面结合的 Maspin 直接控制膀胱癌细胞黏附于血管壁。阻断这一过程可能防止跨内皮迁移和肿瘤细胞扩散。因此，下调表面结合的 Maspin 可能成为预防肿瘤扩散到远处器官的一种选择。
