Epithelial Tumor Invasiveness Ornithine Decarboxylase Overexpression Leads to Increased

Ornithine decarboxylase (ODC) overexpression cooperates with genetic lesions such as an activated c@rashta to enhance epithelial tumorigenesis. To assess the invasiveness of ODC-overexpressing cells, two noninvasive epi dermal cell lines, nontumorigenic BK-i cells, and the papilloma-derived cell line SP-i were infected with a replication-defective retrovirus that overexpresses ODC, inoculated into deepithelialized rat tracheas, and transplanted into athymic nude mice. After 5 weeks, ODC-overexpressing BK-i cells remainedlocalizedon the luminal surface of the tracheal xenotransplants, whereas the ODC-overexpressing SP-i celis were ex tremely invasive, with the whole tracheal wall penetrated. This invasive ness of ODC-overexpressing SP-i cells was accompanied by elevated proteinase expression, including increased urokinase plasminogen activa tor activity in ODC-overexpressingcells and elevated stromelysin-i mRNA expression in the stromal cells of invaded tracheal transplants.