Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression.
Angiogenesis, an essential process for tumor growth, is regulated by endothelial proliferation factors and their inhibitors such as endostatin. Endostatin, a carboxyl-terminal fragment of type XVIII collagen, inhibits endothelial proliferation, angiogenesis, and tumor growth. Ornithine decarboxylase (ODC), a molecule that is overexpressed in various cancers, is associated with promoting tumor growth and angiogenesis. We found that ODC-overexpressing human cancer cells and breast cancer specimens showed suppressed expression of type XVIII collagen and endostatin. We hypothesized that ODC overexpression may facilitate angiogenesis in tumors by suppressing endostatin expression. ODC-overexpressing COS cells, which showed suppressed type XVIII collagen and endostatin expression, were established. Conditioned media derived from these cells, containing decreased levels of endostatin, induced significant endothelial proliferation. ODC-overexpressing cells, when transplanted into nude mice, suppressed type XVIII collagen expression and promoted neovascularization in vivo. Thus, overexpression of ODC facilitates endothelial proliferation by suppressing endostatin expression.
Nemoto
Takahiro
T
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Japan.
Hori
Hisae
H
Yoshimoto
Masataka
M
Seyama
Yousuke
Y
Kubota
Shunichiro
S
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002417:Cattle; D002455:Cell Division; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043170:Collagen Type XVIII; D043169:Endostatins; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism; D014162:Transfection
D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen; D009955:Ornithine Decarboxylase