A Kleber1, R W Hartmann, J Jose. 1. Pharmazeutische und Medizinische Chemie, Naturwissenschaftlich-Technische Fakultät III, Universität des Saarlandes, Saarbrücken, Germany.
Abstract
PURPOSE: A broad body of evidence indicates the involvement of P450 TxA2 (thromboxane A2 synthetase) in tumor metastasis formation. A distinct function of the enzyme in this multistep process, however, is still unknown. Therefore the effect of TxA2 (thromboxane A2) on tumor cell adhesion to the basement membrane, a key event in metastasis formation, was investigated. METHODS: A wide variety of compounds designed in our work group and identified as P450 TxA2 inhibitors were applied to several P450 TxA2-positive tumor cell lines to test their influence on tumor cell adhesion. For this purpose an in-vitro basement membrane adhesion model with the matrix gel preparation Matrigel was used. RESULTS: Most of the P450 TxA2 inhibitors tested had no effect on cell adhesion. Although two compounds significantly reduced tumor cell adhesion in a concentration-dependent manner, this was not related to P450 TxA2 inhibition. CONCLUSION: These data indicate that TxA2 might not be involved in the attachment of tumor cell lines to the basement membrane.
PURPOSE: A broad body of evidence indicates the involvement of P450 TxA2 (thromboxane A2 synthetase) in tumor metastasis formation. A distinct function of the enzyme in this multistep process, however, is still unknown. Therefore the effect of TxA2 (thromboxane A2) on tumor cell adhesion to the basement membrane, a key event in metastasis formation, was investigated. METHODS: A wide variety of compounds designed in our work group and identified as P450 TxA2 inhibitors were applied to several P450 TxA2-positive tumor cell lines to test their influence on tumor cell adhesion. For this purpose an in-vitro basement membrane adhesion model with the matrix gel preparation Matrigel was used. RESULTS: Most of the P450 TxA2 inhibitors tested had no effect on cell adhesion. Although two compounds significantly reduced tumor cell adhesion in a concentration-dependent manner, this was not related to P450 TxA2 inhibition. CONCLUSION: These data indicate that TxA2 might not be involved in the attachment of tumor cell lines to the basement membrane.