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: Prasenohadi Pradono, Ryushi Tazawa, Makoto Maemondo, Masashi Tanaka, Kazuhiro Usui, Yasuo Saijo, Koichi Hagiwara, Toshihiro Nukiwa
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 1 Pg. 63-6 (Jan 01 2002) ISSN: 0008-5472 [Print] United States
• PMID: 11782360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytochrome P-450 Enzyme System
• Intramolecular Oxidoreductases
• prostacyclin synthetase
• Thromboxane-A Synthase

Topics

• Adenocarcinoma (blood supply, enzymology, genetics, therapy)
• Animals
• Cell Division (genetics)
• Colonic Neoplasms (blood supply, enzymology, genetics, pathology, therapy)
• Cytochrome P-450 Enzyme System (genetics)
• Female
• Intramolecular Oxidoreductases (genetics)
• Mice
• Mice, Inbred BALB C
• Neovascularization, Pathologic (enzymology, genetics, pathology, therapy)
• Thromboxane-A Synthase (genetics)
• Transduction, Genetic (methods)