Vanaja D K, Grossmann M E, Celis E, Young C Y
Department of Urology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Cancer Res. 2000 Sep 1;60(17):4714-8.
The biological modifier delta12-prostaglandin J2 and related prostaglandins have been reported to have significant growth-inhibitory activity with induction of heat shock proteins (Hsps). Tumor-derived Hsps have been shown previously to elicit specific immunity to tumors from which they are isolated. In this study, 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2)-induced Hsp70 was purified from transgenic adenocarcinoma mouse prostate cells (TRAMP-C2). It was then tested for its ability to activate specific CTLs and induce protective immunity against prostate cancer in C57BL/6 mice. Treatment of cells with 8.0 microM 15d-PGJ2 for 24 h caused significant induction of Hsp70 expression. The yield of Hsp70 purified from 15d-PGJ2-treated cells was 4-5-fold higher when compared with untreated TRAMP-C2 cells. Vaccination of mice with Hsps isolated from TRAMP-C2 cells elicited tumor-specific CTLs and prevented the growth of TRAMP-C2 tumors. These results indicate that the induced heat shock proteins may have promising applications for antitumor, T-cell immunotherapy. In particular, these findings have important implications for the development of novel anticancer therapies aimed at promoting an immune response to prostate tumors.
据报道，生物修饰剂δ12 - 前列腺素J2及相关前列腺素具有显著的生长抑制活性，并能诱导热休克蛋白（Hsps）。此前已表明，肿瘤来源的热休克蛋白能引发针对其来源肿瘤的特异性免疫。在本研究中，从转基因腺癌小鼠前列腺细胞（TRAMP - C2）中纯化出15 - 脱氧 - δ12,14 - 前列腺素J2（15d - PGJ2）诱导的Hsp70。然后测试其激活特异性细胞毒性T淋巴细胞（CTLs）以及在C57BL / 6小鼠中诱导针对前列腺癌的保护性免疫的能力。用8.0微摩尔/升的15d - PGJ2处理细胞24小时可显著诱导Hsp70表达。与未处理的TRAMP - C2细胞相比，从15d - PGJ2处理的细胞中纯化出的Hsp70产量高出4 - 5倍。用从TRAMP - C2细胞中分离出的热休克蛋白对小鼠进行疫苗接种可引发肿瘤特异性CTLs，并阻止TRAMP - C2肿瘤的生长。这些结果表明，诱导产生的热休克蛋白可能在抗肿瘤T细胞免疫治疗中具有广阔的应用前景。特别是，这些发现对于开发旨在促进针对前列腺肿瘤的免疫反应的新型抗癌疗法具有重要意义。
