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Suppression of pulmonary metastasis using adenovirally motility related protein-1 (MRP-1/CD9) gene delivery

Abstract

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-β-gal vector (103.2±8.5 days vs 71.2±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.

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Abbreviations

MAb:

monoclonal antibody

rAd:

recombinant adenovirus

β-gal:

β-galactosidase

CD:

white cell differentiation antigen

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Acknowledgements

We thank Tatsuya Hirai for his technical assistance, Mitsuko Shirata for her assistance in preparation of the manuscript, and Dr Oobayasi for his pathological examination. This work was supported in part by Grants-in-Aid from the Ministry of Education, Science Sports and Culture of Japan to M Miyake (No 12470280) and the Vehicle Racing Commemorative Foundation to M Miyake.

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Miyake, M., Inufusa, H., Adachi, M. et al. Suppression of pulmonary metastasis using adenovirally motility related protein-1 (MRP-1/CD9) gene delivery. Oncogene 19, 5221–5226 (2000). https://doi.org/10.1038/sj.onc.1203919

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