Yamaguchi Hiroshi, Tanaka Fumiaki, Sadanaga Noriaki, Ohta Mitsuhiko, Inoue Hiroshi, Mori Masaki
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 874-0838 Beppu, Japan.
Int J Oncol. 2003 Dec;23(6):1697-702.
The widespread expression of CD40, a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, is likely to account for the central role of CD40 in the regulation of humoral immunity and host defense. Interestingly, the expression of the CD40 in various types of carcinoma cells was often observed and conveys signals regulating diverse cellular responses, ranging from proliferation to growth suppression. Thus, the biologic role of the CD40-CD40L interaction in solid tumors is still controversial. In this study, we investigated the expression and function of the CD40 in gastric carcinoma cells. In 3-4,5 dimethylthiozol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin V/propidium iodide staining, CD40 stimulation using a soluble form of CD40 ligand did not affect cell viability, but significantly inhibited Fas-mediated or chemotherapy-mediated apoptosis in three CD40-positive gastric cancer cell lines. Moreover, in migration assay, CD40 stimulation induced an elevation of cell motility in CD40-positive gastric carcinoma cells. Our results show that the CD40 expression on gastric carcinoma makes cells less vulnerable to apoptosis induced by Fas or chemotherapy. These results suggest that the CD40 expression on gastric carcinoma may be associated with cell survival and elevation of cell motility.
肿瘤坏死因子（TNF）受体（TNFR）超家族成员CD40的广泛表达，可能是其在体液免疫调节和宿主防御中发挥核心作用的原因。有趣的是，经常观察到CD40在各种类型癌细胞中的表达，并传递调节从增殖到生长抑制等多种细胞反应的信号。因此，CD40-CD40L相互作用在实体瘤中的生物学作用仍存在争议。在本研究中，我们调查了CD40在胃癌细胞中的表达和功能。在3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）试验和膜联蛋白V/碘化丙啶染色中，使用可溶性形式的CD40配体刺激CD40，对细胞活力没有影响，但显著抑制了三种CD40阳性胃癌细胞系中Fas介导的或化疗介导的细胞凋亡。此外，在迁移试验中，CD40刺激导致CD40阳性胃癌细胞的细胞运动性升高。我们的结果表明，胃癌细胞上的CD40表达使细胞对Fas或化疗诱导的凋亡更具抗性。这些结果表明，胃癌上的CD40表达可能与细胞存活和细胞运动性升高有关。
