BACKGROUND Endothelial progenitor cells (EPCs) are regarded as promising targeted vectors for delivering therapeutic genes or agents in cancer therapy. The purpose of this study was to investigate the role of intravenously administered KAI1/CD82 genetically transduced EPCs in the tumorigenesis and metastasis of nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS EPCs were isolated from human umbilical cord blood, expanded in culture, and stably transduced with lentiviral vectors expressing KAI1/CD82. The KAI1/CD82 EPCs were injected intravenously into nude mice bearing human NPC xenografts. Tumor growth and the incidence of liver and lung metastases were observed. Expression of KAI1/CD82 was determined by immunofluorescent staining. RESULTS The NPC model was successfully established. Tumor growth was not suppressed when mice were injected with KAI1/CD82 EPCs (KAI1/CD82 EPCs group) compared with when non-transduced EPCs was present (EPCs group) or the control (1.485±0.234, 1.388±0.204, and 1.487±0.223g, respectively; P>0.05). However, the incidence of lung metastasis was significantly reduced in the KAI1/CD82+ EPCs group compared with the EPCs group and the control group (10%, 55% and 45%, respectively; P=0.005), and there was a significant decrease in the number of metastatic foci on the lung surface (17.50±3.54, 34.27±5.35, and 38.44±9.63 respectively; P=0.007). Moreover, KAI1/CD82 was expressed in lung metastatic foci of the KAI1/CD82 EPCs group, but not in the EPCs group and control group. CONCLUSIONS EPCs can be used as a delivery vehicle for suppressor genes KAI1/CD82 to NPC, and the migration of KAI1/CD82 genetically engineered EPCs can inhibit NPC lung metastasis in a mouse model.