Kost E R, Herzog T J, Adler L M, Williams S, Mutch D G
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Am J Obstet Gynecol. 1996 Jan;174(1 Pt 1):145-53. doi: 10.1016/s0002-9378(96)70387-3.
Our purpose was to define the expression of tumor necrosis factor receptors on ovarian cancer cells and determine what role these receptors play in tumor necrosis factor-alpha-mediated cytolysis.
Cell surface expression of tumor necrosis factor-alpha receptors was determined on ovarian cancer cell lines Caov-3, SK-OV-3, NIH:OVCAR-3, and A2780 by a tumor necrosis factor-alpha-binding assay that used iodine 125-labeled tumor necrosis factor-alpha. Monoclonal antibodies specific for the 55 to 60 kd (TR60) and 75 to 80 kd (TR80) tumor necrosis factor receptors were used to determine the relative density of each receptor type. To elucidate which receptor(s) was responsible for mediating the signal for cytolysis, 24-hour MTT cytolytic assays that used tumor necrosis factor-alpha and emetine were performed in the presence or absence of receptor-specific monoclonal antibodies.
The four ovarian cell lines expressed a similar number of surface receptors, 4500 to 7000 per cell, had similar dissociation constants, 0.3 to 0.6 nmol/L, and expressed predominately the TR60 receptor subtype. Receptor function studies showed that the presence of the monoclonal antibody to the TR60 receptor completely inhibited tumor necrosis factor-alpha-mediated cytolysis, whereas the monoclonal antibody to the TR80 receptor only partially blocked cytolysis.
Ovarian cancer cell lines express both tumor necrosis factor receptors, with the TR60 receptor being the dominant subtype. Tumor necrosis factor-alpha-mediated cytolysis appears to be dependent on the presence of a functional TR60 receptor. The TR80 receptor does not appear requisite for cytolysis; however, a complementary role cannot be excluded. Manipulation of tumor necrosis factor receptor subtypes on ovarian cancer cells may enhance the cytotoxic effects, thus improving the therapeutic efficacy of tumor necrosis factor-alpha.
我们的目的是确定肿瘤坏死因子受体在卵巢癌细胞上的表达情况，并确定这些受体在肿瘤坏死因子-α介导的细胞溶解中所起的作用。
通过使用碘125标记的肿瘤坏死因子-α的肿瘤坏死因子-α结合试验，测定卵巢癌细胞系Caov-3、SK-OV-3、NIH:OVCAR-3和A2780上肿瘤坏死因子-α受体的细胞表面表达。使用针对55至60kd（TR60）和75至80kd（TR80）肿瘤坏死因子受体的单克隆抗体来确定每种受体类型的相对密度。为了阐明哪种受体负责介导细胞溶解信号，在存在或不存在受体特异性单克隆抗体的情况下，进行了使用肿瘤坏死因子-α和依米丁的24小时MTT细胞溶解试验。
四种卵巢细胞系表达的表面受体数量相似，每个细胞有4500至7000个，解离常数相似，为0.3至0.6nmol/L，并且主要表达TR60受体亚型。受体功能研究表明，针对TR60受体的单克隆抗体的存在完全抑制了肿瘤坏死因子-α介导的细胞溶解，而针对TR80受体的单克隆抗体仅部分阻断了细胞溶解。
卵巢癌细胞系表达两种肿瘤坏死因子受体，其中TR60受体是主要亚型。肿瘤坏死因子-α介导的细胞溶解似乎依赖于功能性TR60受体的存在。TR80受体似乎不是细胞溶解所必需的；然而，不能排除其互补作用。操纵卵巢癌细胞上的肿瘤坏死因子受体亚型可能会增强细胞毒性作用，从而提高肿瘤坏死因子-α的治疗效果。
