PDF(Pubmed)
Abstract：
Recently, the need to develop a robust three-dimensional (3D) cell culture system that serves as a valuable in vitro tumor model has been emphasized. This system should closely mimic the tumor growth behaviors observed in vivo and replicate the key elements and characteristics of human tumors for the effective discovery and development of anti-tumor therapeutics. Therefore, in this study, we developed an effective 3D in vitro model of human prostate cancer (PC) using a marine collagen-based biomimetic 3D scaffold. The model displayed distinctive molecular profiles and cellular properties compared with those of the 2D PC cell culture. This was evidenced by (1) increased cell proliferation, migration, invasion, colony formation, and chemoresistance; (2) upregulated expression of crucial multidrug-resistance- and cancer-stemness-related genes; (3) heightened expression of key molecules associated with malignant progressions, such as epithelial-mesenchymal transition transcription factors, Notch, matrix metalloproteinases, and pluripotency biomarkers; (4) robust enrichment of prostate cancer stem cells (CSCs); and (5) enhanced expression of integrins. These results suggest that our 3D in vitro PC model has the potential to serve as a research platform for studying PC and prostate CSC biology, as well as for screening novel therapies targeting PC and prostate CSCs.
摘要：
最近,强调了开发强大的三维（3D）细胞培养系统作为有价值的体外肿瘤模型的必要性。该系统应紧密模拟体内观察到的肿瘤生长行为，并复制人类肿瘤的关键要素和特征，以有效发现和开发抗肿瘤疗法。因此,在这项研究中，我们使用基于海洋胶原蛋白的仿生3D支架开发了一种有效的人类前列腺癌（PC）3D体外模型。与2DPC细胞培养物相比，该模型显示出独特的分子谱和细胞特性。这可以通过（1）细胞增殖增加来证明，迁移,入侵,菌落形成,和化学耐药；（2）上调关键多药耐药和癌症干性相关基因的表达；（3）与恶性进展相关的关键分子的表达升高，如上皮-间质转化转录因子，缺口,基质金属蛋白酶,和多能性生物标志物;(4)前列腺癌干细胞(CSC)的稳健富集;和(5)整合素的增强表达。这些结果表明，我们的3D体外PC模型有可能作为研究PC和前列腺CSC生物学的研究平台，以及筛选针对PC和前列腺CSC的新疗法。
