title: Effect of thyroid hormone-nitric oxide interaction on tumor growth, angiogenesis, and aminopeptidase activity in mice.
abstract: This study evaluated the effects of thyroid hormone-NO interaction on tumor development, vascularization, vascular endothelial growth factor (VEGF), and aminopeptidase (AP) activity in a murine model of implanted Lewis's carcinoma. Experiments were performed in male CBA-C57 mice. Animals were untreated (controls) or treated with: T4, the antithyroid drug methimazole, the NO inhibitor L-NAME, T4+L-NAME, methimazole+NAME, the αvß3 integrin antagonist tetrac, T4+tetrac, the iNOS inhibitor aminoguanidine (AG), and T4 + AG; all treatments were for 6 weeks except for tetrac, administered for the last 11 days. Mice were subcutaneously inoculated with 1 × 10(6) exponentially growing Lewis carcinoma 3LL cells into the dorsum. Study variables 9 days later were tumor weight (TW), Hb content, an index of tumor vascularization, VEGF, and AP activity. T4 produced parallel increases in TW and angiogenesis. L-NAME reduced TW and angiogenesis in control, hyperthyroid, and hypothyroid mice, whereas AG had no effect on these variables. Tetrac arrested TW in normal and T4-treated mice but did not decrease angiogenesis in T4-treated animals. Negative correlations were found between TW and AP activity in tumors from control hyper- and hypothyroid groups and an inverse relationship was observed between TW and AP activities in tetrac-treated mice. T4 enhances TW and angiogenesis, in which NO participates, but requires activation of integrin αvß3 to promote carcinogenesis. NO blockade reduces TW, regardless of the thyroid status. Thyroid hormone negatively modulates AP activity in the tumor. Accordingly, blockade of the membrane TH receptor αvß3 integrin reduces TW associated with an increase in AP activity.
authors.affiliation: Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Carmona-Cortés
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez-Gómez
authors.forename: Rosemary
authors.initials: R
authors.lastname: Wangensteen
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Banegas
authors.forename: Ángel M
authors.initials: ÁM
authors.lastname: García-Lora
authors.forename: Andrés
authors.initials: A
authors.lastname: Quesada
authors.forename: Antonio
authors.initials: A
authors.lastname: Osuna
authors.forename: Félix
authors.initials: F
authors.lastname: Vargas
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D049109:Cell Proliferation; D006146:Guanidines / Q000494:pharmacology; D006454:Hemoglobins / Q000032:analysis; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D013963:Thyroid Hormones / Q000502:physiology*; D013974:Thyroxine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D006146:Guanidines; D006454:Hemoglobins; D013963:Thyroid Hormones; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000626:Aminopeptidases; C011126:tetraiodothyroacetic acid; D013974:Thyroxine; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester