No effect of thromboxane A₂ on the attachment of tumor cell lines MDA MB 231, DU145, and U937 to the basement membrane in an in-vitro model.

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.