title: Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth.
abstract: Cyclooxygenase, involved in tumor growth and angiogenesis, converts arachidonic acid to prostaglandin (PG)H(2), which is immediately converted to bioactive prostanoids including PGE(2), PGD(2), thromboxane (TX)A(2) and PGI(2). To test the hypothesis that changes in the prostanoid profile alter cancer growth, we transduced the retroviral vectors carrying TXA(2) synthase cDNA or PGI(2) synthase cDNA to colon-26 adenocarcinoma cells and subsequently inoculated each transformant to syngeneic BALB/c mice. Tumors derived from TXA(2) synthase transformants grew faster (280%, day 8, versus null-vector control; P < 0.05) and showed more abundant vasculature (204%, versus null-vector control; P < 0.01), whereas tumors from PGI(2) synthase transformants presented opposite effects. These effects by the transgenes were reversed by administration of specific inhibitors. These results suggest that the profile of downstream metabolites of cyclooxygenase in cancer cells can be a determinant for tumor development.
authors.affiliation: Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Prasenohadi
authors.initials: P
authors.lastname: Pradono
authors.forename: Ryushi
authors.initials: R
authors.lastname: Tazawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Usui
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Saijo
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D000818:Animals; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D013930:Thromboxane-A Synthase / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase