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 TxA 2 (thromboxane A 2 synthetase) in tumor metastasis formation. A distinct function of the enzyme in this multistep process, however, is still unknown. Therefore the eect of TxA 2 (thromboxane A 2 ) 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 identi®ed as P450 TxA 2 inhibitors were applied to several P450 TxA 2 -positive tumor cell lines to test their in¯uence 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 TxA 2 inhibitors tested had no eect on cell adhesion. Although two compounds signi®cantly reduced tumor cell adhesion in a concentration-dependent manner, this was not related to P450 TxA 2 inhibition. Conclusion: These data indicate that TxA 2 might not be involved in the attachment of tumor cell lines to the basement membrane.Keywords P450 TxA 2 á Inhibitors á Metastasis á Tumor cell adhesion á Basement membrane Materials and methodsCell lines U937 (promonocytic human cell line) and DU145 (epithelial-like, adherent cell line, established from a prostate adenocarcinoma metastasis) were obtained from the DSMZ (Braunschweig, Germany).

Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer

“…In cancer cells, including breast cancer cells, TBXA2R has been shown not to influence the adhesion of cancer cells to matrix proteins [ 10 ]. Interestingly, TBXA2R has been shown to influence angiogenesis in a lung tumour model, potentially by affecting the migration of endothelial cells [ 11 ].…”