近日，瑞士苏黎世联邦理工学院的Dagmar Iber及其研究团队取得一项新进展。他们揭示了上皮性膀胱癌发病时的形态学和力学不稳定性。相关研究成果已于2025年1月7日在国际知名学术期刊《自然—物理学》上发表。

据悉，上皮组织的恶性肿瘤，称为癌，占据了大多数癌症病例。研究主要集中于将不同的癌亚型与基因突变相关联。然而，癌的进展不仅涉及信号网络的重新布线，还伴随着上皮细胞和细胞外基质的力学变化。

该研究团队在膀胱癌初期发现了基底膜的复杂形态变化，并提出这些变化是由于上皮细胞过度增生引发的力学不稳定性所致。研究人员对小鼠和人类的膀胱组织进行了成像，并进行了差异性生长模拟，发现不同黏膜层的刚度变化可导致组织形态异常。

由此产生的增厚、皱褶和折叠与早期乳头状瘤和原位癌相似。原子力显微镜证实了病理状态下基底膜的局部刚度变化。这项研究结果揭示了不同膀胱癌亚型可能的力学起源，并可能为未来的治疗和预防策略提供指导。

附：英文原文

Title: Morphometry and mechanical instability at the onset of epithelial bladder cancer

Author: Lampart, Franziska L., Vetter, Roman, Yamauchi, Kevin A., Wang, Yifan, Runser, Steve, Strohmeyer, Nico, Meer, Florian, Hussherr, Marie-Didie, Camenisch, Gieri, Seifert, Hans-Helge, Rentsch, Cyrill A., Le Magnen, Clmentine, Mller, Daniel J., Bubendorf, Lukas, Iber, Dagmar

Issue&Volume: 2025-01-07

Abstract: Malignancies of epithelial tissues, called carcinomas, account for most cancer cases. Research has largely focused on correlating different carcinoma subtypes to genetic alterations. However, as well as a rewiring in the signalling networks, carcinoma progression is accompanied by mechanical changes in the epithelial cells and the extracellular matrix. Here we reveal intricate morphologies in the basement membrane at the onset of bladder cancer and propose that they emerge from a mechanical instability upon epithelial overgrowth. We imaged mouse and human bladder tissue and performed differential growth simulations, and found that stiffness changes in the different mucosa layers can result in aberrant tissue morphologies. The resulting thickening, wrinkles and folds resemble early papillary tumours and carcinomas in situ. Atomic force microscopy confirmed local stiffness changes in the pathological basement membrane. Our findings suggest a possible mechanical origin of the different bladder carcinoma subtypes and may guide future developments in treatment and prophylaxis.

DOI: 10.1038/s41567-024-02735-2

Source: https://www.nature.com/articles/s41567-024-02735-2