Center for Molecular Medicine, University of Connecticut Health Center , Farmington, CT 06030-3101 , USA.
Biol Open. 2012 Jul 15;1(7):622-8. doi: 10.1242/bio.2012653. Epub 2012 May 9.
Ovarian cancer is the most lethal gynaecologic cancer, in large part because of its early dissemination and rapid development of chemotherapy resistance. Spheroids are clusters of tumor cells found in the peritoneal fluid of patients that are thought to promote this dissemination. Current models suggest that spheroids form by aggregation of single tumor cells shed from the primary tumor. Here, we demonstrate that spheroids can also form by budding directly as adherent clusters from a monolayer. Formation of budded spheroids correlated with expression of vimentin and lack of cortical E-cadherin. We also found that compared to cells grown in monolayers, cells grown as spheroids acquired progressive resistance to the chemotherapy drugs Paclitaxel and Cisplatin. This resistance could be completely reversed by dissociating the spheroids. Our observations highlight a previously unappreciated mode of spheroid formation that might have implications for tumor dissemination and chemotherapy resistance in patients, and suggest that this resistance might be reversed by spheroid dissociation.
卵巢癌是妇科癌症中最致命的一种，在很大程度上是因为它早期的扩散和对化疗的快速耐药性。球体是在患者的腹腔液中发现的一簇肿瘤细胞，被认为促进了这种扩散。目前的模型表明，球体是由从原发性肿瘤脱落的单个肿瘤细胞聚集形成的。在这里，我们证明球体也可以通过直接从单层贴壁簇出芽形成。出芽球体的形成与波形蛋白的表达和皮质 E-钙粘蛋白的缺乏相关。我们还发现，与单层培养的细胞相比，作为球体培养的细胞对化疗药物紫杉醇和顺铂的耐药性逐渐增强。通过分离球体可以完全逆转这种耐药性。我们的观察结果强调了一种以前未被认识到的球体形成模式，这可能对患者的肿瘤扩散和化疗耐药性有影响，并表明这种耐药性可以通过球体解离来逆转。
