Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression

• Published in: Blood Vol. 99; no. 4; pp. 1478 - 1481
• Main Authors: Nemoto, Takahiro, Hori, Hisae, Yoshimoto, Masataka, Seyama, Yousuke, Kubota, Shunichiro
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.02.2002; The Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cattle; Cell Division; Collagen - antagonists & inhibitors; Collagen - metabolism; Collagen Type XVIII; COS Cells; Endostatins; Endothelium, Vascular - cytology; Endothelium, Vascular - enzymology; Endothelium, Vascular - metabolism; Female; General aspects; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Neoplasms - enzymology; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic - chemically induced; Neovascularization, Pathologic - enzymology; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase - metabolism; Ornithine Decarboxylase - physiology; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - metabolism; Pulmonary Artery - cytology; Pulmonary Artery - metabolism; Transfection; Tumors; Human; Endothelial cell; Enzyme; Endostatin; Gene overexpression; Lyases; Malignant hemopathy; Ornithine decarboxylase; Malignant tumor; Gene expression; In vitro; Invasion; Mechanism; Endothelium; Angiogenesis; Carbon-carbon lyases; Enzymatic activity; Carboxy-lyases; Established cell line; High malignancy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.4.1478

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.