Reciprocal interactions between prostate epithelial cells and their adjacent stromal microenvironment not only are essential for tissue homeostasis but also play a key role in tumor development and progression. Malignant transformation is associated with the formation of a reactive stroma where cancer-associated fibroblasts (CAFs) induce matrix remodeling and thereby provide atypical biochemical and biomechanical signals to epithelial cells. Previous work has been focused on the cellular and molecular phenotype as well as on matrix stiffness and remodeling, providing potential targets for cancer therapeutics. So far, biomechanical changes in CAFs and adjacent epithelial cells of the prostate have not been explored. Here, we compared the mechanical properties of primary prostatic CAFs and patient-matched non-malignant prostate tissue fibroblasts (NPFs) using atomic force microscopy (AFM) and real-time deformability cytometry (RT-FDC). It was found that CAFs exhibit an increased apparent Young's modulus, coinciding with an altered architecture of the cytoskeleton compared with NPFs. In contrast, co-cultures of benign prostate epithelial (BPH-1) cells with CAFs resulted in a decreased stiffness of the epithelial cells, as well as an elongated morphological phenotype, when compared with co-cultures with NPFs. Moreover, the presence of CAFs increased proliferation and invasion of epithelial cells, features typically associated with tumor progression. Altogether, this study provides novel insights into the mechanical interactions between epithelial cells with the malignant prostate microenvironment, which could potentially be explored for new diagnostic approaches.

前列腺上皮细胞与其相邻的基质微环境之间的相互作用不仅是组织稳态所必需的，而且在肿瘤的发生和发展中也起着关键作用。恶性转化与反应性基质的形成有关，在该基质中，癌症相关的成纤维细胞（CAF）诱导基质重塑，从而向上皮细胞提供非典型的生化和生物力学信号。先前的工作集中在细胞和分子表型以及基质刚度和重塑上，为癌症治疗提供了潜在的靶标。到目前为止，尚未研究CAF和前列腺邻近上皮细胞的生物力学变化。这里，我们使用原子力显微镜（AFM）和实时变形性细胞术（RT-FDC）比较了原发性前列腺CAF和患者匹配的非恶性前列腺组织成纤维细胞（NPF）的机械性能。已经发现，CAF与NPF相比，表现出增加的表观杨氏模量，这与细胞骨架的结构改变相吻合。相比之下，与NPF的共培养相比，良性前列腺上皮（BPH-1）细胞与CAF的共培养导致上皮细胞的硬度降低，并且形态表型延长。而且，CAF的存在增加了上皮细胞的增殖和侵袭，这通常与肿瘤的进展有关。共，