Extracellular matrix (ECM) tumorigenic alterations resulting in high matrix deposition and stiffening are hallmarks of adenocarcinomas and are collectively defined as desmoplasia. Here, we thoroughly analysed primary prostate cancer tissues obtained from numerous patients undergoing radical prostatectomy to highlight reproducible structural changes in the ECM leading to the loss of the glandular architecture. Starting from patient cells, we established prostate cancer tumoroids (PCTs) and demonstrated they require TGF-β signalling pathway activity to preserve phenotypical and structural similarities with the tissue of origin. By modulating TGF-β signalling pathway in PCTs, we unveiled its role in ECM accumulation and remodelling in prostate cancer. We also found that TGF-β-induced ECM remodelling is responsible for the initiation of prostate cell epithelial-to-mesenchymal transition (EMT) and the acquisition of a migratory, invasive phenotype. Our findings highlight the cooperative role of TGF-β signalling and ECM desmoplasia in prompting prostate cell EMT and promoting tumour progression and dissemination.

导致高基质沉积和硬化的细胞外基质 (ECM) 致瘤改变是腺癌的标志，统称为结缔组织增生。在这里，我们彻底分析了从众多接受根治性前列腺切除术的患者中获得的原发性前列腺癌组织，以突出 ECM 中导致腺体结构丧失的可重复结构变化。从患者细胞开始，我们建立了前列腺癌类肿瘤 (PCT)，并证明它们需要 TGF-β 信号通路活性来保持与起源组织的表型和结构相似性。通过调节 PCT 中的 TGF-β 信号通路，我们揭示了其在前列腺癌 ECM 积累和重塑中的作用。我们还发现 TGF-β 诱导的 ECM 重塑负责前列腺细胞上皮间质转化 (EMT) 的启动以及迁移性、侵袭性表型的获得。我们的研究结果强调了 TGF-β 信号传导和 ECM结缔组织形成在促进前列腺细胞 EMT 和促进肿瘤进展和扩散中的协同作用。