ORNITHINE DECARBOXYLASE IS DIRECTLY INVOLVED IN MOUSE MAMMARY-CARCINOMA CELL INVASION IN-VITRO

To elucidate the role of ornithine decarboxylase (ODC) in cancer cell invasion, we have compared the invasiveness of mouse mammary carcinoma, FM3A and its variant cell line, EXOD, which overproduces ODC. We have found that EXOD cells showed about 5.6-fold more invasiveness through a reconstituted basement membrane (Matrigel) compared to FM3A cells. To elucidate the underlying mechanism of increased invasiveness of EXOD cells, we analyzed gelatinase activity in conditioned media derived from FM3A and EXOD cells. EXOD cells secreted approximately 3-fold 72kDa gelatinase compared to FM3A cells. Cell attachment ability to Matrigel was also studied. Although FM3A and EXOD cells showed increased attachment to Matrigel in a dose-dependent manner, EXOD cells showed higher cell attachment ability compared to FM3A cells. Anti-72kDa gelatinase neutralizing antibody suppressed EXOD cell invasion through Matrigel. Further, antisense oligonucleotides of ODC suppressed EXOD cell invasion through Matrigel. Although the causal relationship among ODC expression, gelatinase secretion and cell attachment ability remains to be elucidated, the results suggest that both overproduction of ODC and 72kDa gelatinase secretion are directly involved in increased invasiveness of EXOD cells. (C) 1995 Academic Press, Inc.