Ornithine decarboxylase overexpression leads to increased epithelial tumor invasiveness
Smith, M.K.; Goral, M.A.; Wright, J.H.; Matrisian, L.M.; Morris, R.J.; Klein-Szanto, A.J.; Gilmour, S.K.
Cancer Research 57(11): 2104-2108
1997
ISSN/ISBN: 0008-5472 PMID: 9187103 Document Number: 470357
Ornithine decarboxylase (ODC) overexpression cooperates with genetic lesions such as an activated c-ras-Ha to enhance epithelial tumorigenesis. To assess the invasiveness of ODC-overexpressing cells, two noninvasive epidermal cell lines, nontumorigenic BK-1 cells, and the papilloma-derived cell line SP-1 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-1 cells remained localized on the luminal surface of the tracheal xenotransplants, whereas the ODC-overexpressing SP-1 cells were extremely invasive, with the whole tracheal wall penetrated. This invasiveness of ODC-overexpressing SP-1 cells was accompanied by elevated proteinase expression, including increased urokinase plasminogen activator activity in ODC-overexpressing cells and elevated stromelysin-1 mRNA expression in the stromal cells of invaded tracheal transplants.