In vivo tumor delivery of the green fluorescent protein gene to report future occurrence of metastasis

The green fluorescent protein (GFP) gene was administered to intraperitonea lly (i.p.) growing human stomach cancer in nude mice to visualize future re gional and distant metastases. GFP retroviral supernatants were injected i. p, from day 4 to day 10 after i.p. implantation of the cancer cells. Tumor and metastasis fluorescence was visualized every other week with the use of fluorescence optics via a laparotomy on the tumor-bearing animals. At 2 we eks after retroviral GFP delivery, GFP-expressing tumor cells were observed in gonadal fat, greater omentum, and intestine, indicating that these prim ary i.p. growing tumors were efficiently transduced by the GFP gene and cou ld be visualized by its expression. At the second and third laparotomies, G FP-expressing tumor cells were observed to have spread to lymph nodes in th e mesentery and other regional sires. At the fourth laparotomy, widespread tumor growth was visualized by GFP expression, inducing liver metastasis. N o normal tissues were found to be transduced by the GFP retrovirus. Thus, r eporter gene transduction of the primary tumor enabled detection of its sub sequent metastasis. This gene therapy model could be applied to primary tum ors before resection or other treatment to have a fluorescent early detecti on system for metastasis and recurrence.