Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.
Urology & Nephrology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Mol Biol Rep. 2021 May;48(5):4253-4262. doi: 10.1007/s11033-021-06440-8. Epub 2021 Jun 4.
Cells translate the mechanosensing of extracellular matrix component dysregulation and stiffness into the signal transduction including Osteopontin (OPN) through the Hippo pathway. But how extracellular matrix (ECM) component dysregulation and stiffness are ultimately linked to transitional cell carcinoma (TCC) development remains poorly understood. This study was aimed to evaluate the possible links between ECM component alteration after cancer surgery and OPN and Yes-associated protein (YAP) expression in TCC and adjacent tissues. In this study, we used 50 TCC (25 newly diagnosed and 25 recurrent) and 50 adjacent tissues to determine the tissue stiffness using atomic force microscopy. The mRNA expression of SPP1, Indian hedgehog (IHH), and YAP was also determined using qRT-PCR. Western blotting and ELISA were performed to assess the tissue and serum levels of OPN, respectively. To assess the glycoproteins and elastic fibers content, Periodic Acid Schiff, and Verhoeff-Van Gieson Staining were performed, respectively. Matrix stiffness was markedly higher in TCCs than adjacent tissues (p < 0.05). Gene expression analysis showed that YAP, SPP1, and IHH genes were upregulated in TCC tissues (p < 0.05). Additionally, the OPN protein overexpression was observed in the tissue and the serum of TCC patients (p < 0.05). We also found that glycoproteins, elastic fibers content of recurrent TCC tissues was remarkably higher as compared to adjacent tissues (p < 0.05). Our results suggest that glycoproteins and elastic fibers content modulation and ECM stiffness may upregulates the expression of YAP, SPP1 and IHH genes, and possibly contribute to the TCC development and relapse.
细胞通过 Hippo 通路将细胞外基质成分失调和刚性的机械感觉转化为信号转导，包括骨桥蛋白（OPN）。但是，细胞外基质（ECM）成分失调和刚性如何最终与移行细胞癌（TCC）的发展相关联仍知之甚少。本研究旨在评估癌症手术后 ECM 成分改变与 TCC 及相邻组织中 OPN 和 Yes 相关蛋白（YAP）表达之间的可能联系。在这项研究中，我们使用了 50 例 TCC（25 例新诊断和 25 例复发）和 50 例相邻组织，使用原子力显微镜测定组织刚性。还使用 qRT-PCR 测定 SPP1、印度刺猬（IHH）和 YAP 的 mRNA 表达。进行 Western 印迹和 ELISA 分别评估 OPN 的组织和血清水平。为了评估糖蛋白和弹性纤维含量，分别进行了过碘酸希夫（Periodic Acid Schiff）和 Verhoeff-Van Gieson 染色。TCC 中的基质刚性明显高于相邻组织（p<0.05）。基因表达分析显示，YAP、SPP1 和 IHH 基因在 TCC 组织中上调（p<0.05）。此外，在 TCC 患者的组织和血清中观察到 OPN 蛋白过表达（p<0.05）。我们还发现，与相邻组织相比，复发性 TCC 组织中的糖蛋白和弹性纤维含量明显增加（p<0.05）。我们的结果表明，糖蛋白和弹性纤维含量的调节以及 ECM 刚性可能会上调 YAP、SPP1 和 IHH 基因的表达，并可能有助于 TCC 的发展和复发。
