Suppression of pulmonary metastasis using adenovirally motility related protein-1 (MRP-1/CD9) gene delivery.
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.
Miyake
M
M
Department of Thoracic Surgery and Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka 530-8480, Japan.
Inufusa
H
H
Adachi
M
M
Ishida
H
H
Hashida
H
H
Tokuhara
T
T
Kakehi
Y
Y
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division; D002465:Cell Movement; D005121:Extremities; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008545:Melanoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D015996:Survival Rate; D060245:Tetraspanin 29; D014162:Transfection; D019076:Transgenes / Q000235:genetics; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29