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PMID:9630216

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Citation

Tsujii, M, Kawano, S, Tsuji, S, Sawaoka, H, Hori, M and DuBois, RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705-16

Abstract

To explore the role of cyclooxygenase (COX) in endothelial cell migration and angiogenesis, we have used two in vitro model systems involving coculture of endothelial cells with colon carcinoma cells. COX-2-overexpressing cells produce prostaglandins, proangiogenic factors, and stimulate both endothelial migration and tube formation, while control cells have little activity. The effect is inhibited by antibodies to combinations of angiogenic factors, by NS-398 (a selective COX-2 inhibitor), and by aspirin. NS-398 does not inhibit production of angiogenic factors or angiogenesis induced by COX-2-negative cells. Treatment of endothelial cells with aspirin or a COX-1 antisense oligonucleotide inhibits COX-1 activity/expression and suppresses tube formation. Cyclooxygenase regulates colon carcinoma-induced angiogenesis by two mechanisms: COX-2 can modulate production of angiogenic factors by colon cancer cells, while COX-1 regulates angiogenesis in endothelial cells.

Links

PubMed

Keywords

Animals; Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Antineoplastic Agents/pharmacology; Caco-2 Cells; Carcinoma/blood supply; Carcinoma/pathology; Cell Communication; Cell Movement; Coculture Techniques; Colonic Neoplasms/blood supply; Colonic Neoplasms/pathology; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors/pharmacology; Endothelium, Vascular/cytology; Endothelium, Vascular/growth & development; Growth Substances/biosynthesis; Humans; Isoenzymes/metabolism; Membrane Proteins; Mice; Mice, Nude; Molecular Sequence Data; Neoplasms, Experimental/blood supply; Neovascularization, Pathologic; Prostaglandin-Endoperoxide Synthases/metabolism; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:PGH2

involved_in

GO:0090050: positive regulation of cell migration involved in sprouting angiogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PGH2

involved_in

GO:0010575: positive regulation of vascular endothelial growth factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PGH2

involved_in

GO:0071636: positive regulation of transforming growth factor beta production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PGH2

involved_in

GO:0045429: positive regulation of nitric oxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PGH2

involved_in

GO:0090362: positive regulation of platelet-derived growth factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PGH2

involved_in

GO:0090271: positive regulation of fibroblast growth factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PGH2

involved_in

GO:0010575: positive regulation of vascular endothelial growth factor production

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P35355

P

Seeded From UniProt

complete

HUMAN:PGH2

involved_in

GO:0045429: positive regulation of nitric oxide biosynthetic process

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P35355

P

Seeded From UniProt

complete

HUMAN:PGH2

involved_in

GO:0071636: positive regulation of transforming growth factor beta production

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P35355

P

Seeded From UniProt

complete

HUMAN:PGH2

involved_in

GO:0090050: positive regulation of cell migration involved in sprouting angiogenesis

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P35355

P

Seeded From UniProt

complete

HUMAN:PGH2

involved_in

GO:0090271: positive regulation of fibroblast growth factor production

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P35355

P

Seeded From UniProt

complete


See also

References

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