ADENOVIRUS-MEDIATED GENE-TRANSFER OF FIBROBLAST GROWTH-FACTOR-I - ANGIOGENESIS AND TUMORIGENICITY IN NUDE-MICE

Gene transfer of angiogenic growth factors with replication-deficient recombinant adenovirus (Ad) vectors may provide a new approach to the treatment of ischemic diseases. To determine if Ad-infected cells coul d stimulate angiogenesis in vivo and to assess the tumorigenicity of c ells infected with these vectors, NIH3T3 fibroblasts infected with Ad vectors coding for human acidic fibroblast growth factor (aFGF-I) were used in angiogenic and tumorigenic assays. Infected cells induced a s trong angiogenic response in vivo, while cells infected with control v irus did not, Stable 3T3 transfectants expressing the FCF-I gene were also highly angiogenic and exhibited growth in soft agar, while Ad-inf ected cells did not, Ad-infected cells grew transiently in nude mice, whereas 3T3 transfectants formed large tumors which grew exponentially , Extrapolation of cell dose-response curves showed that a minimum of 1.5 x 10(4) infected cells were required for transient tumor cell grow th in vivo, Ad-infected cells cultured in vitro for 30 days lost their invasive phenotype and the ability for transient cell growth in nude mice. Thus, phenotypic changes induced by Ad-mediated gene transfer of FGF-I are transient both in vitro and in vivo, suggesting that these Ad vectors do not have tumorigenic potential, Stimulation of angiogene sis by Ad-infected cells may be useful for the evaluation of anti-angi ogenic and anti-tumor agents. (C) 1997 Wiley-Liss, Inc.