Ovarian cancer is the most lethal gynecological cancer, where survival rates have had modest improvement over the last 30 years. Metastasis of cancer cells is a major clinical problem, and patient mortality occurs when ovarian cancer cells spread beyond the confinement of ovaries. Disseminated ovarian cancer cells typically spread within the abdomen, where ascites accumulation aids in their transit. Metastatic ascites contain multicellular spheroids, which promote chemo-resistance and recurrence. However, little is known about the origin and mechanisms through which spheroids arise. Using live-imaging of 3D culture models and animal models, we report that epithelial ovarian cancer (EOC) cells, the most common type of ovarian cancer, can spontaneously detach as either single cells or clusters. We report that clusters are more resistant to anoikis and have a potent survival advantage over single cells. Using in vivo lineage tracing, we found that multicellular spheroids arise preferentially from collective detachment, rather than aggregation in the abdomen. Finally, we report that multicellular spheroids from collective detachment are capable of seeding intra-abdominal metastases that retain intra-tumoral heterogeneity from the primary tumor.

中文翻译：

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多细胞脱离在上皮性卵巢癌的腹腔内传播过程中产生转移性球体。

卵巢癌是最致命的妇科癌症，在过去30年中，其存活率已有一定程度的改善。癌细胞的转移是一个主要的临床问题，当卵巢癌细胞扩散到卵巢以外时，就会导致患者死亡。弥漫性卵巢癌细胞通常在腹腔内扩散，腹水在那里积聚有助于其转移。转移性腹水含有多细胞球体，可促进化学耐药性和复发。但是，对球体产生的起源和机理知之甚少。使用3D文化模型和动物模型的实时成像，我们报告说，上皮性卵巢癌（EOC）细胞是最常见的卵巢癌类型，可以自发分离成单个细胞或成簇。我们报告说，群集对单核细胞具有更强的抵抗力，并且比单细胞具有强大的生存优势。使用体内谱系追踪，我们发现多细胞球体优先产生于集体脱离，而不是腹部聚集。最后，我们报道了来自集体脱离的多细胞球体能够播种保留原发肿瘤的肿瘤内异质性的腹腔内转移。