Ornithine decarboxylase overexpression leads to increased epithelial tumor invasiveness.
Ornithine decarboxylase (ODC) overexpression cooperates with genetic lesions such as an activated c-rasHa 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.
Smith
M K
MK
Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096, USA.
Goral
M A
MA
Wright
J H
JH
Matrisian
L M
LM
Morris
R J
RJ
Klein-Szanto
A J
AJ
Gilmour
S K
SK
D000818:Animals; D010450:Endopeptidases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D017403:In Situ Hybridization; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D010212:Papilloma / Q000201:enzymology* / Q000235:genetics; D051381:Rats; D017154:Stromal Cells / Q000378:metabolism; D014132:Trachea / Q000637:transplantation / Q000821:virology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D019278:Matrix Metalloproteinase 3; D009955:Ornithine Decarboxylase