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初级纤毛在膀胱癌进展和侵袭中的存在及其意义。

Primary cilia presence and implications in bladder cancer progression and invasiveness.

机构信息

Department of Human Anatomy and Histology, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.

Institute for Health Research Aragón (IIS), Domingo Miral s/n, 50009, Zaragoza, Spain.

出版信息

Histochem Cell Biol. 2021 May;155(5):547-560. doi: 10.1007/s00418-021-01965-2. Epub 2021 Jan 25.

Abstract

Urothelial bladder cancer is the tenth most common cancer worldwide. It is divided into muscle and non-muscle invading bladder cancer. Primary cilia have been related to several cancer hallmarks such as proliferation, epithelial-to-mesenchymal transition (EMT) or tumoral progression mainly through signaling pathways as Hedgehog (Hh). In the present study, we used immunohistochemical and ultrastructural techniques in human tissues of healthy bladder, non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) to study and clarify the activation of epithelial-to-mesenchymal transition and Hedgehog signaling pathway and the presence of primary cilia. Thus, we found a clear correlation between EMT and Hedgehog activation and bladder cancer stage and progression. Moreover, we identified the presence of primary cilia in these tissues. Interestingly, we found that in NMIBC, some ciliated cells cross the basement membrane and localized in lamina propria, near blood vessels. These results show a correlation between EMT beginning from urothelial basal cells and primary cilia assembly and suggest a potential implication of this structure in tumoral migration and invasiveness (likely in a Hh-dependent way). Hence, primary cilia may play a fundamental role in urothelial bladder cancer progression and suppose a potential therapeutic target.

摘要

膀胱癌是全球第十大常见癌症。它分为肌肉浸润性膀胱癌和非肌肉浸润性膀胱癌。初级纤毛与几种癌症特征有关,如增殖、上皮-间充质转化(EMT)或肿瘤进展,主要通过 Hedgehog(Hh)等信号通路。在本研究中,我们使用免疫组织化学和超微结构技术研究了健康膀胱、非肌肉浸润性膀胱癌(NMIBC)和肌肉浸润性膀胱癌(MIBC)的人类组织,以研究和阐明上皮-间充质转化和 Hedgehog 信号通路的激活以及初级纤毛的存在。因此,我们发现 EMT 和 Hedgehog 激活与膀胱癌的分期和进展之间存在明显的相关性。此外,我们在这些组织中发现了初级纤毛的存在。有趣的是,我们发现 NMIBC 中的一些纤毛细胞穿过基底膜并定位于固有层,靠近血管。这些结果表明 EMT 始于尿路上皮基底层和初级纤毛组装之间存在相关性,并表明该结构可能在肿瘤迁移和侵袭性方面具有潜在的意义(可能以 Hh 依赖性的方式)。因此,初级纤毛可能在尿路上皮膀胱癌的进展中发挥重要作用,并构成潜在的治疗靶点。

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