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Gene Transfer of Thromboxane A₂ Synthase and Prostaglandin I₂ Synthase Antithetically Altered Tumor Angiogenesis and Tumor Growth¹

Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan

Cyclooxygenase, involved in tumor growth and angiogenesis, converts arachidonic acid to prostaglandin (PG)H₂, which is immediately converted to bioactive prostanoids including PGE₂, PGD₂, thromboxane (TX)A₂ and PGI₂. To test the hypothesis that changes in the prostanoid profile alter cancer growth, we transduced the retroviral vectors carrying TXA₂ synthase cDNA or PGI₂ synthase cDNA to colon-26 adenocarcinoma cells and subsequently inoculated each transformant to syngeneic BALB/c mice. Tumors derived from TXA₂ 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 PGI₂ 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.

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