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Evaluation of the Interaction Between TGF β and Nitric Oxide in the Mechanisms of Progression of Colon Carcinoma

Lohm, Sylvia ; Peduto-Eberl, Lucie ; Lagadec, Patricia ; Renggli-Zulliger, Nicole ; Dudler, Jean ; Jeannin, Jean-François ; Juillerat-Jeanneret, Lucienne

In: Clinical & Experimental Metastasis, 2005, vol. 22, no. 4, p. 341-349

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    Titre
    • Evaluation of the Interaction Between TGF β and Nitric Oxide in the Mechanisms of Progression of Colon Carcinoma
    Auteur
    • Lohm, Sylvia. University Institute of Pathology, Bugnon 25, CH-1011, Lausanne, Switzerland
    • Peduto-Eberl, Lucie. University Institute of Pathology, Bugnon 25, CH-1011, Lausanne, Switzerland
    • Lagadec, Patricia. Cancer Immunotherapy Research Laboratory, Ecole Pratique des Hautes Etudes, INSERM U517, France
    • Renggli-Zulliger, Nicole. Division of Rhumatology, CHUV, Lausanne, Switzerland
    • Dudler, Jean. Division of Rhumatology, CHUV, Lausanne, Switzerland
    • Jeannin, Jean-François. Cancer Immunotherapy Research Laboratory, Ecole Pratique des Hautes Etudes, INSERM U517, France
    • Juillerat-Jeanneret, Lucienne. University Institute of Pathology, Bugnon 25, CH-1011, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Clinical & Experimental Metastasis, 2005, vol. 22, no. 4, p. 341-349. Kluwer Academic Publishers
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:310275
    Summary
    It is recognised that stromal cells determine cancer progression. We have previously shown that active TGFβ produced by rat colon carcinoma cells modulated NO production in rat endothelial cells. To elucidate the role of TGFβ and NO in the mechanisms of interaction of colon carcinoma cells with stromal cells and in cancer progression, we transfected REGb cells, a regressive colon carcinoma clone secreting latent TGFβ, with a cDNA encoding for a constitutively-secreted active TGFβ. Out of 20 injected rats only one tumour progressed, which was resected and sub-cultured (ReBeta cells). ReBeta cells secreted high levels of active TGFβ. The adhesive properties of REGb and Rebeta cells to endothelial cells were similar, showing that the secretion of active TGFβ is not involved in tumour cell adhesion to endothelial cells. ReBeta, but not REGb, cell culture supernatants inhibited cytokine-dependent NO secretion by endothelial cells, but inhibition of NO production was similar in co-cultures of REGb or ReBeta cells with endothelial cells. Therefore, secretion of active TGFβ regulated endothelial NO synthase activity when tumour cells were distant from, but not in direct contact with, endothelial cells. However, only ReBeta cells inhibited cytokine-dependent secretion of NO in coculture with macrophages, indicating that the active-TGFβ-NO axis confers an advantage for tumour cells in their interaction with macrophages rather than endothelial cells in cancer progression