Breast cancer, a leading cause of cancer-related deaths globally, exhibits distinct subtypes with varying pathological, genetic, and clinical characteristics. Despite advancements in breast cancer treatments, its histological and molecular heterogeneity pose a significant clinical challenge. Triple-negative breast cancer (TNBC), a highly aggressive subtype lacking targeted therapeutics, adds to the complexity of breast cancer treatment. Recent years have witnessed the development of advanced 3D culture technologies, such as organoids and spheroids, providing more representative models of healthy human tissue and various malignancies. These structures, resembling organs in structure and function, are generated from stem cells or organ-specific progenitor cells via self-organizing processes. Notably, 3D culture systems bridge the gap between 2D cultures and in vivo studies, offering a more accurate representation of in vivo tumors’ characteristics. Exosomes, small nano-sized molecules secreted by breast cancer and stromal/cancer-associated fibroblast cells, have garnered significant attention. They play a crucial role in cell-to-cell communication, influencing tumor progression, invasion, and metastasis. The 3D culture environment enhances exosome efficiency compared to traditional 2D cultures, impacting the transfer of specific cargoes and therapeutic effects. Furthermore, 3D exosomes have shown promise in improving therapeutic outcomes, acting as potential vehicles for cancer treatment administration. Studies have demonstrated their role in pro-angiogenesis and their innate therapeutic potential in mimicking cellular therapies without side effects. The 3D exosome model holds potential for addressing challenges associated with drug resistance, offering insights into the mechanisms underlying multidrug resistance and serving as a platform for drug screening. This review seeks to emphasize the crucial role of 3D culture systems in studying breast cancer, especially in understanding the involvement of exosomes in cancer pathology.
乳腺癌作为全球癌症相关死亡的主要原因,其不同亚型在病理学、遗传学和临床特征上存在显著差异。尽管乳腺癌治疗已取得进展,但其组织学和分子异质性构成了重大的临床挑战。三阴性乳腺癌作为一种高度侵袭性且缺乏靶向治疗手段的亚型,进一步增加了乳腺癌治疗的复杂性。近年来,以类器官和球状体为代表的先进三维培养技术不断发展,为构建更贴近健康人体组织及各类恶性肿瘤特征的模型提供了新途径。这些在结构和功能上模拟器官的三维结构,可通过干细胞或器官特异性祖细胞的自组织过程生成。值得注意的是,三维培养系统填补了二维培养与体内研究之间的空白,能更准确地呈现体内肿瘤的特征。由乳腺癌细胞及基质/癌相关成纤维细胞分泌的外泌体作为纳米级微小分子受到广泛关注,它们在细胞间通讯中发挥关键作用,影响肿瘤进展、侵袭和转移过程。相较于传统二维培养,三维培养环境能提升外泌体效能,影响特定物质的传递及治疗效果。此外,三维外泌体在改善治疗效果方面展现出潜力,可作为癌症治疗的潜在递送载体。研究表明其在促血管生成中发挥作用,并具有模拟细胞疗法而无副作用的天然治疗潜力。三维外泌体模型有望为解决耐药性问题提供新思路,既能揭示多药耐药机制,又可作为药物筛选平台。本综述旨在强调三维培养系统在乳腺癌研究中的关键作用,特别是在解析外泌体参与癌症病理进程方面的重要意义。
Advances in 3D Culture Models to Study Exosomes in Triple-Negative Breast Cancer