Rakowicz-Szulczynska E M, McIntosh D G, Smith M L
Departments of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
Clin Diagn Lab Immunol. 1999 Jan;6(1):115-26. doi: 10.1128/CDLI.6.1.115-126.1999.
Ovarian cancer cells were isolated from ascites fluid of 30 different patients diagnosed with cystadenocarcinoma of ovaries. Large colonies of malignant ASC cells were observed during the first week of cell growth in vitro. Colony formation was followed by fusion of cells and formation of large multinucleated and highly vacuolated syncytia. In contrast, cells isolated from the ascites fluid produced by patients with benign mucinous cystadenoma of ovaries did not form syncytia. Nonmalignant Brenner tumor cells, isolated from the ascites fluid, also did not form syncytia. Syncytia, but not the nonmalignant tumor cells, were immunofluorescence stained with an anti-human immunodeficiency virus type 1 (HIV-1) gp120 monoclonal antibody (MAb) and MAb RAK-BrI. Both MAbs recognized cancer-associated antigens RAK (for Rakowicz markers) p120, p42, and p25. Exposure of ASC cells to either the anti-HIV-1 gp120 MAb or MAb RAK-BrI inhibited syncytium formation. PCR with HIV-1 Env-derived primers revealed DNA sequences with over 90% homology to HIV-1 gp41 in syncytia and in ovarian cancer cells but not in normal ovary cells. Electron microscopic analysis revealed viral particles, hexagonal in shape (90 nm in diameter), with a dense central core surrounded by an inner translucent capsid and dense outer shell with projections. Negative staining detected membrane-covered particles (100 to 110 nm in diameter) in the cell culture medium. Incubation of normal breast cells with viral particles resulted in drastic morphological changes and syncytium formation by the transformed breast cells. The cytopathic effects of the identified virus resembled those of spumaviruses, which, in addition to their epitopic and genetic homology to HIV-1, might suggest a common phylogeny.
从30例被诊断为卵巢囊腺癌的不同患者的腹水中分离出卵巢癌细胞。在体外细胞生长的第一周观察到大量恶性ASC细胞集落。集落形成后细胞融合并形成大型多核且高度空泡化的多核体。相比之下，从卵巢良性黏液性囊腺瘤患者腹水中分离出的细胞未形成多核体。从腹水中分离出的非恶性勃勒纳瘤细胞也未形成多核体。多核体而非非恶性肿瘤细胞，用抗人免疫缺陷病毒1型（HIV-1）gp120单克隆抗体（MAb）和MAb RAK-BrI进行免疫荧光染色。两种单克隆抗体均识别癌症相关抗原RAK（针对拉科维茨标志物）p120、p42和p25。将ASC细胞暴露于抗HIV-1 gp120单克隆抗体或MAb RAK-BrI均可抑制多核体形成。用HIV-1 Env衍生引物进行的PCR显示，在多核体和卵巢癌细胞中存在与HIV-1 gp41具有超过90%同源性的DNA序列，但在正常卵巢细胞中未检测到。电子显微镜分析显示病毒颗粒呈六边形（直径90nm），有一个致密的中央核心，周围是一个内部半透明衣壳和带有突起的致密外壳。负染色在细胞培养基中检测到膜覆盖颗粒（直径100至110nm）。用病毒颗粒孵育正常乳腺细胞会导致转化的乳腺细胞发生剧烈形态变化并形成多核体。所鉴定病毒的细胞病变效应类似于泡沫病毒，除了它们与HIV-1的表位和基因同源性外，这可能暗示了共同的系统发育。
