Miyake M, Inufusa H, Adachi M, Ishida H, Hashida H, Tokuhara T, Kakehi Y
Department of Thoracic Surgery and Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka 530-8480, Japan.
Oncogene. 2000 Nov 2;19(46):5221-6. doi: 10.1038/sj.onc.1203919.
Previously we showed that MRP-1/CD9 might prevent tumor metastasis by suppression of cell motility and invasion of tissue barriers. The present study explored the possibility of preventing metastasis of mouse melanoma BL6 by expression of MRP-1/CD9 through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of MRP-1/CD9 cDNA. Intratumor injection of an adenovirus vector (rAd-MRP-1/CD9) expressing MRP-1/CD9 resulted in a 73.7% reduction in the number of pulmonary metastases of mice and the median survival time of mice treated with rAd-MRP-1/CD9 was significantly longer than those treated with the rAd-beta-gal vector (103.2 approximately plus;8.5 days vs 71.2 approximately plus;5.2 days, P<0.001 respectively). These results support the expression of MRP-1/CD9 through gene transfer as a therapeutic strategy for preventing metastases and prolonging survival, and support the feasibility of gene transfer in a clinically relevant setting.
此前我们发现,多药耐药相关蛋白-1/CD9(MRP-1/CD9)可能通过抑制细胞运动性和侵袭组织屏障来预防肿瘤转移。本研究通过基因转移表达MRP-1/CD9,探讨了预防小鼠黑色素瘤BL6转移的可能性。使用复制缺陷型腺病毒载体进行MRP-1/CD9 cDNA的体内转移。瘤内注射表达MRP-1/CD9的腺病毒载体(rAd-MRP-1/CD9)可使小鼠肺转移瘤数量减少73.7%,且接受rAd-MRP-1/CD9治疗的小鼠中位生存时间显著长于接受rAd-β-半乳糖苷酶载体治疗的小鼠(分别为103.2±8.5天和71.2±5.2天,P<0.001)。这些结果支持通过基因转移表达MRP-1/CD9作为预防转移和延长生存期的治疗策略,并支持在临床相关环境中进行基因转移的可行性。