Bladder cancer cells orchestrate tumour progression by pro-inflammatory cytokines. Cytokines modulate the local tumour microenvironment and increase the susceptibility of tumour distant tissues for metastasis. Here, we investigated the impact of human bladder cancer cell derived factors on the ability to modulate and activate human vascular endothelial cells. The pro-inflammatory and pro-coagulatory potential of four different bladder cancer cell lines was accessed by qRT-PCR arrays and ELISA. Modulation and activation of endothelial cells was studied in microfluidic devices. Clinical relevance of our findings was confirmed by immune histology in tissue samples of bladder cancer patients and public transcriptome data. The unbalanced ratio between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1ra) in the secretome of bladder cancer cells converted the quiescent vascular endothelium into a pro-adhesive, pro-inflammatory, and pro-coagulatory surface. Microfluidic experiments showed that tumour cell induced endothelial cell activation promoted leukocyte recruitment and platelet adhesion. Human bladder cancer tissue analysis confirmed that loss of IL-1ra and elevated IL-1 expression was associated with enhanced cancer progression. Our data indicate that IL-1 and IL-1ra were dysregulated in bladder cancer and could facilitate tumour dissemination through endothelial cell activation. Targeting the IL-1/IL-1ra axis might attenuate tumour-mediated inflammation and metastasis formation.

中文翻译：

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膀胱癌衍生的白介素-1将血管内皮转化为促炎和促凝表面

膀胱癌细胞通过促炎细胞因子来协调肿瘤的进展。细胞因子调节局部肿瘤微环境，并增加肿瘤远处组织转移的敏感性。在这里，我们调查了人类膀胱癌细胞衍生因子对调节和激活人类血管内皮细胞的能力的影响。通过qRT-PCR阵列和ELISA获得了四种不同膀胱癌细胞系的促炎和促凝潜能。在微流体装置中研究了内皮细胞的调节和激活。膀胱癌患者组织样本中的免疫组织学和公共转录组数据证实了我们研究结果的临床意义。膀胱癌细胞分泌组中白介素（IL）-1和IL-1受体拮抗剂（IL-1ra）之间的不平衡比例将静止的血管内皮转化为促粘附，促炎和促凝的表面。微流体实验表明，肿瘤细胞诱导的内皮细胞活化促进白细胞募集和血小板粘附。人膀​​胱癌组织分析证实，IL-1ra的丧失和IL-1表达的升高与癌症进展加快有关。我们的数据表明，IL-1和IL-1ra在膀胱癌中表达失调，可通过内皮细胞激活促进肿瘤扩散。靶向IL-1 / IL-1ra轴可能会减弱肿瘤介导的炎症和转移形成。和促凝表面。微流体实验表明，肿瘤细胞诱导的内皮细胞活化促进白细胞募集和血小板粘附。人膀​​胱癌组织分析证实，IL-1ra的丧失和IL-1表达的升高与癌症进展加快有关。我们的数据表明，IL-1和IL-1ra在膀胱癌中表达失调，可通过内皮细胞激活促进肿瘤扩散。靶向IL-1 / IL-1ra轴可能会减弱肿瘤介导的炎症和转移形成。和促凝表面。微流体实验表明，肿瘤细胞诱导的内皮细胞活化促进白细胞募集和血小板粘附。人膀​​胱癌组织分析证实，IL-1ra的丧失和IL-1表达的升高与癌症进展加快有关。我们的数据表明，IL-1和IL-1ra在膀胱癌中表达失调，可通过内皮细胞激活促进肿瘤扩散。靶向IL-1 / IL-1ra轴可能会减弱肿瘤介导的炎症和转移形成。人膀​​胱癌组织分析证实，IL-1ra的丧失和IL-1表达的升高与癌症进展加快有关。我们的数据表明，IL-1和IL-1ra在膀胱癌中表达失调，可通过内皮细胞激活促进肿瘤扩散。靶向IL-1 / IL-1ra轴可能会减弱肿瘤介导的炎症和转移形成。人膀​​胱癌组织分析证实，IL-1ra的丧失和IL-1表达的升高与癌症进展加快有关。我们的数据表明，IL-1和IL-1ra在膀胱癌中表达失调，可通过内皮细胞激活促进肿瘤扩散。靶向IL-1 / IL-1ra轴可能会减弱肿瘤介导的炎症和转移形成。