Tumor angiogenesis, a pivotal process for
cancer growth and
metastasis, requires both upregulation of pro‑angiogenic molecules and downregulation of anti‑angiogenic molecules. Anti-angiogenesis
therapy represents a promising way for
cancer treatment.
Tumstatin, a novel endogenous
angiogenesis inhibitor, inhibits endothelial cell proliferation,
pathological angiogenesis and
tumor growth.
Ornithine decarboxylase (ODC), overexpressed in various
cancers, is associated with cell transformation,
tumor invasion and angiogenesis. We found that the expression of
tumstatin was suppressed in ODC-overexpressing human
cancer cells and
renal carcinoma tissues. We presumed that ODC overexpression may downregulate the expression of
tumstatin. To be able to test this hypothesis, we generated HEK293 cells that overexpress ODC (ODC transfectants) and characterized the following experimental groups: PBS-treated group, mock transfectants, ODC transfectants, ODC transfectants transfected with pcDNA-ODCr (an antisense ODC-expressing plasmid) group and
putrescine-treated group. The effect of ODC overexpression on
tumstatin expression was examined by
reverse transcriptase-polymerase chain reaction (RT-PCR), western blot analysis and dual
luciferase reporter assay. ODC-overexpressing cells and
putrescine-treated cells showed suppressed
tumstatin mRNA and
protein expression, and decreased
tumstatin gene promoter activity. Thus, ODC overexpression suppresses the expression of
tumstatin, which may provide fundamental evidence for the combination of anti-angiogenic
therapy and conventional
therapy for
cancer treatment.