Around 20–30% of ovarian cancer patients exhibit chemoresistance, but there are currently no methods to predict whether a patient will respond to chemotherapy. Here, we discovered that chemoresistant ovarian cancer cells exhibit enhanced survival in a quiescent state upon experiencing the stress of physical confinement. When immobilized in stiff silica gels, most ovarian cancer cells die within days, but surviving cells exhibit hallmarks of single‐cell dormancy. Upon extraction from gels, the cells resume proliferation but demonstrate enhanced viability upon reimmobilization, indicating that initial immobilization selects for cells with a higher propensity to enter dormancy. RNA‐seq analysis of the extracted cells shows they have signaling responses similar to cells surviving cisplatin treatment, and in comparison to chemoresistant patient cohorts, they share differentially expressed genes that are associated with platinum‐resistance pathways. Furthermore, these extracted cells demonstrate greater resistance to cisplatin and paclitaxel, despite being proliferative. In contrast, serum starvation and hypoxia could not effectively select for chemoresistant cells upon removal of the environmental stress. These findings demonstrate that ovarian cancer chemoresistance and the ability to enter dormancy are linked, and immobilization rapidly distinguishes chemoresistant cells. This platform could be suitable for mechanistic studies, drug development, or as a clinical diagnostic tool.

中文翻译：

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固定化快速选择具有增强进入休眠能力的化学抗性卵巢癌细胞。

大约 20-30% 的卵巢癌患者表现出化学抗性，但目前没有方法可以预测患者是否会对化疗产生反应。在这里，我们发现化学抗性卵巢癌细胞在经历物理限制的压力后在静止状态下表现出更高的存活率。当固定在坚硬的硅胶中时，大多数卵巢癌细胞会在几天内死亡，但存活的细胞表现出单细胞休眠的特征。从凝胶中提取后，细胞恢复增殖，但在重新固定后表现出增强的活力，表明初始固定选择具有较高进入休眠倾向的细胞。提取细胞的 RNA-seq 分析表明，它们具有与顺铂治疗后存活的细胞相似的信号反应，并且与化学抗性患者队列相比，它们共享与铂耐药途径相关的差异表达基因。此外，这些提取的细胞尽管具有增殖性，但对顺铂和紫杉醇表现出更大的抵抗力。相反，在去除环境压力后，血清饥饿和缺氧不能有效地选择化学抗性细胞。这些发现表明，卵巢癌的化学抗性和进入休眠状态的能力是相关的，固定化可以快速区分化学抗性细胞。该平台可能适用于机理研究、药物开发或作为临床诊断工具。尽管正在增殖。相反，在去除环境压力后，血清饥饿和缺氧不能有效地选择化学抗性细胞。这些发现表明，卵巢癌的化学抗性和进入休眠状态的能力是相关的，固定化可以快速区分化学抗性细胞。该平台可能适用于机理研究、药物开发或作为临床诊断工具。尽管正在增殖。相反，在去除环境压力后，血清饥饿和缺氧不能有效地选择化学抗性细胞。这些发现表明，卵巢癌的化学抗性和进入休眠状态的能力是相关的，固定化可以快速区分化学抗性细胞。该平台可能适用于机理研究、药物开发或作为临床诊断工具。