Abstract:
A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient\'s tumour tissue. Notably, MTC-22 cells, and the patient\'s carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient\'s tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.
摘要:
从46岁的日本妇女中建立了人卵巢透明细胞癌细胞系。这条线,命名为MTC-22,在补充有10%胎牛血清的常规RPMI1640培养基中连续增殖超过6个月,并且已经传代超过50次。MTC-22倍增时间为~18h,这比迄今为止报道的大多数卵巢透明细胞癌细胞系短得多。形态学上,MTC-22细胞表现出多边形形状,并增殖以形成拼图状排列的单层,而没有接触抑制。超微结构,细胞表现出许多胞浆内糖原颗粒和发育良好的线粒体。G带核型分析表明,细胞具有接近四倍体的复杂核型。我们观察到MTC-22细胞中一系列卵巢癌相关分子的表达模式与患者肿瘤组织中的表达模式相同。值得注意的是,MTC-22小区,和病人的癌组织,表达由R-10G和294-1B1单克隆抗体识别的低硫酸角质素硫酸盐,非黏液性卵巢癌的标志,尤其是透明细胞卵巢癌。此外,特征性点突变-ARID1A中的一个,它编码含有AT丰富的相互作用域的蛋白质1A,另一个在PIK3CB,它编码磷酸肌醇3-激酶的催化亚基-在患者的肿瘤组织中可见,并保留在MTC-22细胞中。总的来说,这些发现表明MTC-22细胞可以作为研究卵巢透明细胞癌病理生理学的有价值的工具,特别是带有PIK3CB突变的,以及开发和验证这种危及生命的恶性肿瘤的新诊断和治疗方法。