Yoshida H, Enomoto H, Miyauchi M, Takenaga K, Tanabe M, Ohnuma N, Sakiyama S, Tagawa M
Department of Pediatric Surgery, Chiba University, School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Int J Oncol. 1998 May;12(5):1067-71. doi: 10.3892/ijo.12.5.1067.
We have examined antitumor effect of murine neuroblastoma cells (C1300) retrovirally transduced with interleukin-4 (IL-4) gene in syngeneic A/J and nude mice. Although in vitro proliferation of IL-4-secreting C1300 cells (C1300/IL-4) was not different from that of wild-type cells, the in vivo tumor growth of C1300/IL-4 cells subcutaneously inoculated into immunocompetent A/J mice was retarded compared with that of wild-type cells and consequently, the survival of the A/J mice which received C1300/IL-4 cells was prolonged. In immunodeficient nude mice we observed accelerated growth rate of wild-type tumors in comparison with the tumors developed in A/J mice. In contrast, the tumor growth of C1300/IL-4 cells in nude mice was significantly suppressed and the growth was much slower than that of C1300/IL-4 cells inoculated in A/J mice. Thus, the secretion of IL-4 from tumor cells produced antitumor effect more efficiently in mature T cell-defective hosts than in immunocompetent mice. Our results suggest a possible clinical application of IL-4 expression in tumor cells via genetic manipulations especially in immunocompromised cancer patients.
我们研究了用白细胞介素-4（IL-4）基因逆转录病毒转导的小鼠神经母细胞瘤细胞（C1300）在同基因A/J小鼠和裸鼠中的抗肿瘤作用。虽然分泌IL-4的C1300细胞（C1300/IL-4）的体外增殖与野生型细胞没有差异，但皮下接种到免疫活性A/J小鼠体内的C1300/IL-4细胞的体内肿瘤生长与野生型细胞相比受到抑制，因此，接受C1300/IL-4细胞的A/J小鼠的生存期延长。在免疫缺陷的裸鼠中，我们观察到野生型肿瘤的生长速度比在A/J小鼠中形成的肿瘤快。相反，C1300/IL-4细胞在裸鼠中的肿瘤生长受到显著抑制，且生长速度比接种在A/J小鼠中的C1300/IL-4细胞慢得多。因此，肿瘤细胞分泌的IL-4在成熟T细胞缺陷宿主中比在免疫活性小鼠中更有效地产生抗肿瘤作用。我们的结果表明，通过基因操作在肿瘤细胞中表达IL-4可能具有临床应用价值，特别是在免疫受损的癌症患者中。
