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.
OBJECTIVE
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.


CONCLUSIONS
These data indicate that TxA2 might not be involved in the attachment of tumor cell lines to the basement membrane.
Kleber
A
A
Pharmazeutische und Medizinische Chemie, Naturwissenschaftlich-Technische Fakultät III, Universität des Saarlandes, Saarbrücken, Germany.
Hartmann
R W
RW
Jose
J
J
D001485:Basement Membrane / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D004791:Enzyme Inhibitors; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase