Ovarian cancer metastasizes into peritoneum through dissemination of transformed epithelia as multicellular spheroids. Harvested from the malignant ascites of patients, spheroids exhibit startling features of organization typical to homeostatic glandular tissues: lumen surrounded by smoothly contoured and adhered epithelia. Herein, we demonstrate that cells of specific ovarian cancer lines in suspension, aggregate into dysmorphic solid "moruloid" clusters that permit intercellular movement, cell penetration, and interspheroidal coalescence. Moruloid clusters subsequently mature into "blastuloid" spheroids with smooth contours, a temporally dynamic lumen and immotile cells. Blastuloid spheroids neither coalesce nor allow cell penetration. Ultrastructural examination reveals a basement membrane-like extracellular matrix coat on the surface of blastuloid, but not moruloid, spheroids. Quantitative proteomics reveals down-regulation in ECM protein Fibronectin-1 associated with the moruloid-blastuloid transition; immunocytochemistry also confirms the relocalization of basement membrane ECM proteins: collagen IV and laminin to the surface of blastuloid spheroids. Fibronectin depletion accelerates, and enzymatic basement membrane debridement impairs, lumen formation, respectively. The regulation by ECM dynamics of the morphogenesis of cancer spheroids potentially influences the progression of the disease.

中文翻译：

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细胞外基质介导恶性卵巢球体中的 moruloid-blastuloid 形态动力学。

卵巢癌通过将转化的上皮细胞作为多细胞球体传播而转移到腹膜。从患者的恶性腹水中采集的球体表现出惊人的稳态腺组织典型组织特征：管腔被平滑轮廓和粘附的上皮细胞包围。在这里，我们证明了悬浮的特定卵巢癌细胞系的细胞聚集成畸形的固体“moruoid”簇，允许细胞间运动、细胞穿透和球体间聚结。Moruloid 簇随后成熟为具有平滑轮廓、时间动态内腔和不动细胞的“blastuloid”球体。Blastuloid 球体既不合并也不允许细胞穿透。超微结构检查显示在囊状体表面上存在基底膜样细胞外基质涂层，但不是 Moruloid 球体。定量蛋白质组学显示 ECM 蛋白 Fibronectin-1 的下调与 moruloid-blastuloid 转变相关；免疫细胞化学还证实了基底膜 ECM 蛋白的重新定位：胶原蛋白 IV 和层粘连蛋白在囊胚球体的表面。纤连蛋白消耗加速，酶促基底膜清创分别损害管腔形成。ECM 动力学对癌症球体形态发生的调节可能会影响疾病的进展。免疫细胞化学还证实了基底膜 ECM 蛋白的重新定位：胶原蛋白 IV 和层粘连蛋白在囊胚球体的表面。纤连蛋白消耗加速，酶促基底膜清创分别损害管腔形成。ECM 动力学对癌症球体形态发生的调节可能会影响疾病的进展。免疫细胞化学还证实了基底膜 ECM 蛋白的重新定位：胶原蛋白 IV 和层粘连蛋白在囊胚球体的表面。纤连蛋白消耗加速，酶促基底膜清创分别损害管腔形成。ECM 动力学对癌症球体形态发生的调节可能会影响疾病的进展。