Disaggregation and invasion of ovarian carcinoma ascites spheroids.

Disaggregation and invasion of ovarian carcinoma ascites spheroids.
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DOI:
10.1186/1479-5876-4-6
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发表时间:
2006-01-24
影响因子:
7.4
通讯作者:
Skubitz AP
Skubitz AP
中科院分区:
医学2区
文献类型:
--
作者:
Burleson KM;Boente MP;Pambuccian SE;Skubitz AP

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恶性腹水通常发生在卵巢癌的晚期,由单个和聚集的肿瘤细胞或球体组成。球体通常被用作肿瘤模型来研究药物疗效,并且已经显示出对一些化疗和放射的抗性。然而,关于球状体的粘附或侵袭能力,以及腹水中这种特定的细胞成分是否有助于卵巢癌的传播,我们知之甚少。在这里,我们研究了从7名卵巢癌患者和1名原发性腹膜癌(PPC)患者中回收的腹水球体的侵袭能力。从患者中分离腹水球体,纯化,并由病理学家进行免疫组化分析以确认诊断。设计体外试验以量化球状体在各种细胞外基质上的解聚以及在正常人间皮细胞单层上的传播和侵入。在每个测定中测定细胞增殖和活力,并通过学生t检验证明统计学显著性。来自所有患者腹水样品的球体在细胞外基质组分上解聚,PPC球体能够在I型胶原上完全解聚。此外,所有腹水球状体样品粘附于活的人间皮细胞单层并在其上解聚,通常不侵入它们。然而,PPC腹水球状体和一个卵巢癌腹水球状体样本偶尔在间皮细胞单层中形成侵袭性病灶,提示更具侵袭性的表型。我们在这里提出在体外试验中使用腹水球体,模仿卵巢癌在体内的传播。我们的研究结果表明,腹水细胞内容物的系统研究是必要的,以了解卵巢癌的生物学。
Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient. Ascites spheroids were isolated from patients, purified, and immunohistochemical analyses were performed by a pathologist to confirm diagnosis. In vitro assays were designed to quantify spheroid disaggregation on a variety of extracellular matrices and dissemination on and invasion into normal human mesothelial cell monolayers. Cell proliferation and viability were determined in each assay, and statistical significance demonstrated by the student's t-test. Spheroids from all of the patients' ascites samples disaggregated on extracellular matrix components, with the PPC spheroids capable of complete disaggregation on type I collagen. Additionally, all of the ascites spheroid samples adhered to and disaggregated on live human mesothelial cell monolayers, typically without invading them. However, the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample occasionally formed invasive foci in the mesothelial cell monolayers, suggestive of a more invasive phenotype. We present here in vitro assays using ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results suggest that systematic studies of the ascites cellular content are necessary to understand the biology of ovarian carcinoma.
DOI: 10.1172/jci114784
发表时间: 1990-09-01
影响因子: 15.9
作者:
MILLS, GB;MAY, C;MARKS, A
通讯作者: MARKS, A
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发表时间: 1993-03-01
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发表时间: 2001-01-15
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DOI: 10.1016/j.ygyno.2003.12.034
发表时间: 2004-04-01
影响因子: 4.7
作者:
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通讯作者: Skubitz, APN
DOI: 10.1002/ijc.2910500627
发表时间: 1992-04-01
影响因子: 6.4
作者:
BARDIES, M;THEDREZ, P;CHATAL, JF
通讯作者: CHATAL, JF